TXIT 2018

Question 1

Based on ICRU-83, the Treated Volume (TV) can be best defined as the:

Answer 1

V98%

= Rationale: ICRU 83 suggests that the treated volume—e.g. volume of tissue receiving a “therapeutic dose” of radiation—might be defined by V98%.

Question 2

An electron scattering foil is used in a LINAC to scatter the beam across the treatment field. What is the approximate relative dose in the beam due to x-ray contamination from the foil?

Answer 2

5%

= Rationale: In a modern linac, typical x-ray contamination dose ranges up to 5% for beams up to 20MeV.

Question 3

In addition to abdominal ultrasound, what imaging studies are routinely required for staging a newly diagnosed Stage III Wilms tumor with favorable histology?

Answer 3

Chest CT only

= Rationale: Abdominal ultrasound is preferred at diagnosis for its ability to provide vascular invasion and flow information about the renal vessels as well as delineate the primary tumor extent with non-irradiative means. Chest CT is preferred at diagnosis to delineate any findings concerning for metastatic disease. Given the radiation exposure related to use of CT, many providers will switch to chest x-rays following the initial evaluation. An MRI of the brain is only required for clear cell sarcoma of the kidney, malignant rhabdoid tumors and renal cell carcinoma while bone scans are typically only required for clear cell sarcoma and renal cell carcinoma. References: John A Kalapurakal THE LANCET Oncology; AREN0321; Vol 5 January 2004; 37-46.

Question 4

In the ACOSOG Z6041, patients with cT2N0 rectal adenocarcinoma were treated with preoperative chemoradiation followed by local excision. What was the approximate 3-year DFS?

Answer 4

90%

= Rationale: Patients with clinical T2N0 rectal adenocarcinoma staged by endorectal ultrasound or endorectal coil MRI, measuring less than 4 cm in greatest diameter, involving less than 40% of the circumference of the rectum, located within 8 cm of the anal verge were included in the study. Neoadjuvant chemoradiotherapy consisted of capecitabine (original dose 825 mg/m2 twice daily on days 1-14 and 22-35), oxaliplatin (50 mg/m2 on weeks 1, 2, 4, and 5), and radiation (5 days a week at 1·8 Gy per day for 5 weeks to a dose of 45 Gy, followed by a boost of 9 Gy, for a total dose of 54 Gy) followed by local excision. Because of adverse events during chemoradiotherapy, the dose of capecitabine was reduced to 725 mg/m2 twice-daily, 5 days per week, for 5 weeks, and the boost of radiation was reduced to 5·4 Gy, for a total dose of 50·4 Gy. The estimated 3-year disease-free survival for the intention-to-treat group was 88.2% (95% CI 81·3-95·8), and for the per-protocol group was 86·9% (79.3-953). References: Garcia-Aguilar J. Lancet Oncol. 2015 Nov. p. 16(15):1537-46.

Question 5

In Indelicato et al., Acta Oncologica (2014), what was the rate of symptomatic brainstem toxicity among pediatric brain tumor patients treated with proton therapy who received a maximum brainstem dose > 56.5 Gy?

Answer 5

10%

= Rationale: Answer: B. Although the overall incidence of symptomatic brainstem injury was 3% among the patients treated with proton therapy, subset analysis showed the rate of symptomatic brainstem injury among patients who had tumors of the posterior fossa, had a maximum point dose of D50%>52.3 Gy, or maximum point dose >56.5 Gy was approximately 10%.

Question 6

For low LET irradiation with a high oxygen enhancement ratio (OER) in regions of the tumor, tumor cell killing is:

Answer 6

greatly reduced at 0.5% versus 20% oxygen

= Rationale: Radiation with a high OER, such as X-rays, exhibit enhanced cell kill under aerated conditions and reduced within hypoxic regions. The radiation sensitivity of cells is reduced as the partial pressure of oxygen drops below ~30mm Hg (~5% oxygen). The OER is greatest below this point. Partial pressure of oxygen at ~ 3mm Hg approximates the radiosensitivity halfway between a hypoxic and aerated condition. Thus, cell kill is dependent on oxygen concentration, and will be decreased at partial pressures below 30 mm Hg, certainly at 3 mm Hg. Little increase in radiation sensitivity is seen at partial pressures greater than 30 mm Hg. References: Hall and Giaccia, Radiobiology for the Radiologist, Sixth ed., pages 89 and 113.

Question 7

Involvement of which blood vessel would render a pancreatic mass borderline resectable?\

Answer 7

90 degree involvement of the celiac axis

= Rationale: A borderline resectable lesion is defined as one in which there is a higher likelihood of an incomplete surgical resection. As such, these patients are not good candidates for upfront resection in comparison to patients with resectable lesions. Answer A describes a resectable tumor, as the spleen and its vasculature are resected in a distal pancreatectomy. Answer C is resectable, as contact with the superior mesenteric vein must be >180 degrees in order to confer higher risk of positive margins and qualify as borderline resectable. Answer D involves >180 degrees of the superior mesenteric artery and is unresectable (also known as locally advanced). This patient would not be expected to be resected with negative margins without a response to pre-operative therapy. Answer B is borderline resectable, due to <180 degree involvement of the celiac axis.

Question 8

In the recent OnCoRe registry study of non-operative management for rectal cancer, what was the approximate rate of local tumor regrowth?

Answer 8

35%

= Rationale: In this recent multicenter-registry study from the UK, the authors reported no difference in non-regrowth DFS or OS between surgical resection versus non-operative approach. However, 34% of patients in the non-operative group experienced local regrowth. Of these, 88% were surgically salvaged, emphasizing the need for close post-treatment surveillance with this approach.

Question 9

For mycosis fungoides, the palm plus the digits on one hand represent what percent of body surface area?

Answer 9

1%

= Rationale: The palm and the digits of one hand represent 1% of total body surface area involved, when trying to assess how much of a patient’s skin is involved with mycosis fungoides.

Question 10

What is the limitation of the linear-quadratic (?/?) cell survival model at high levels of cell kill?

Answer 10

Under predicts survival at high doses

= Rationale: At low doses, the linear-quadratic ?/? model does a good job at predicting cell survival. At higher doses while the model will predict a continuous bending of the survival curve, in reality, the curve “straightens” out; i.e. it becomes essentially exponential. This makes the model very useful for predicting outcomes for fractionated treatment regimens where a relatively large number of low dose fractions are used. When one or a small number of high dose fractions are delivered, the ?/? model would tend to under predict survival under conditions similar to SBRT (at high levels of cell kill). Whether this under prediction is sufficiently large to affect treatment outcomes is under debate.

Question 11

A glioma has IDH mutation, p53 mutation, ATRX loss, 1p deletion, and 19q intact. How should this tumor be classified according to the 2016 WHO classification?

Answer 11

Astrocytoma

= Rationale: In the 2016 WHO Classification of Brain Tumors, some of the molecular characteristics of an astrocytoma are: IDH mutation, p53 mutation, ATRX mutation leading to loss, and lack of co-deletion of 1p19q. A single deletion in 1p or 19q is not sufficient to make an oligodendroglioma diagnosis; they must be co-deleted. Furthermore, p53 mutation and ATRX loss together denote an astrocytoma and are largely mutually exclusive from 1p19q co-deletion.

Question 12

What mean dose to the pharyngeal constrictors results in a 20% risk of dysphagia and aspiration?

Answer 12

50 Gy

= Rationale: 50 Gy mean dose to the constrictors results in a 20% risk of dysphagia and aspiration.

Question 13

For cT1N0M0 breast cancer treated with breast-conserving surgery and sentinel lymph node biopsy with 1 of 2 sentinel lymph nodes positive without ECE {pT1cN1a(sn)}, which subsequent locoregional treatment option is best supported by level 1 evidence?

Answer 13

No further axillary surgery and whole breast radiation +/- draining lymphatics

Z-11: RT +/- ALND > no difference
AMAROS: ALND v RT > more LE with ALND

MA20/EORTC 22922 > DFS/DSS benefit to nodal RT

= Rationale: The ACOSOG Z-11 trial enrolled women with T1-T2 clinically node negative breast cancer who underwent breast conserving surgery and SLNBx with 1 or 2 positive nodes. They were randomly assigned to axillary dissection or no further surgery. All patients subsequently received whole breast RT in the supine position, likely encompassing the low axilla in the tangent fields. Axillary dissection increased morbidity (notably lymphedema risk) without improving any oncologic endpoint. The EORTC AMAROS trial enrolled a similar population and randomized them to axillary dissection vs. radiotherapy to the axilla and SCV nodes. The two treatments yielded equivalent rates of regional recurrence and disease-free survival, but the RT arm was superior with regard to lymphedema rates. Therefore, axillary dissection should be omitted for women receiving RT. Also, results from the MA-20 and EORTC 22922 suggest that the addition of regional nodal irradiation in the setting of node-positive breast cancer improved disease-free survival and reduces breast cancer death and should therefore be strongly considered.

Question 14

Regarding role of extrapleural pneumonectomy (EPP) in patients with mesothelioma:

Answer 14

pleurectomy/decortication followed by pleural based IMRT to 45 Gy in 25 fractions has similar outcomes than EPP followed by adjuvant RT

EPP = En blac pleura, pericardium, hemidiaphram ipsilatera, and LUNG

P/D = Pleua + gross tumor (NO lung or diaphragm)

Extended P/D = P/D + ipsi hemidiaphragm and pericardium

Partial pleurectomy = partial pleura removed

= Rationale: A. Sarcomatoid mesothelioma has very poor prognosis and per NCCN is considered a relative contraindication for surgery. Chemotherapy is the appropriate option for these patients, and palliative radiation as indicated. B. Per single institutional experience from MSKCC and a multicentre phase II study that used pleural based IMRT following pleurectomy/decortication for localized mesothelioma is an appropriate and safe option for therapy. Results appear promising and may be safer and more effective than historical data with EPP followed by adjuvant radiation. Typical adjuvant RT dose after EPP with negative margins is 50-54 Gy, while with positive margins is 54-60 Gy.

Question 15

Which systemic therapy in combination with doxorubicin has been shown to improve PFS and OS in patients with advanced or metastatic soft tissue sarcoma?

Answer 15

Olaratumab

= Rationale: In a study of olaratumab and doxorubicin versus doxorubicin for soft tissue sarcoma, the combination showed improvement in overall survival (26.5 vs 14.7 mos) and progressive-free survival (6.6 vs 4.1 mos) compared to doxorubicin alone.

Question 16

Which is accurate regarding different definitive treatment modalities for Stage I seminoma?

Answer 16

Chemotherapy results in a greater proportion of para-aortic nodal failures compared with radiation

= Rationale: In stage I seminoma, whether randomized to one cycle of carboplatin chemotherapy or radiation, 5 year recurrence free survival was very good (95% vs 96%). Patients receiving chemotherapy experienced a higher rate of para-aortic nodal failures (74% vs 9%) while patients receiving radiation had a higher rate of pelvic failures (28% vs 0%).

Question 17

As per the ABS guidelines, the equivalent dose (EQD2) in patients who have not responded well with a residual tumor greater than 4 cm at the time of brachytherapy is?

Answer 17

85 to 90 Gy

= Rationale: The EQD2 is 85-90 Gy in order to maximize local control in tumors greater than 4 cm at the time of implant. The toxicity associated with doses greater than 90 Gy would simply be too high. Doses lower than 80 greater would be inadequate. EQD2 between 80 to 84 are more appropriate for tumors that are less than 4 cm. References: Viswanathan, et al.American Brachytherapy Society consensus guidelines for locally advanced carcinoma of the cervix. Part II: high-dose-rate brachytherapy, 2012 Jan-Feb, Brachytherapy, 11(1), 47-52.

Question 18

Per the RTOG 3-arm randomized trial (91-11), which treatment yielded optimal locoregional control for advanced laryngeal cancer?

Answer 18

ChemoRT to 70 Gy in 35 fractions.

= Rationale: The updated results of RTOG 91-11 continue to demonstrate superior loregional control for eligible patients treated with chemoradiation, albeit without survival difference amongst the three tested arms (IC->RT, ChRT, and RT alone). Appropriate patient selection is key (as in this case, T3N0 disease, good baseline larynx function).

Question 19

For a patient with histologic findings of neoplastic thymic epithelial cells with spindle shape, with great vessel invasion, what is the WHO Histologic Classification and Modified Masaoka stage?

Answer 19

Type A, Stage IIIB

= Rationale: Type A has neoplastic thymic epithelial cells with spindle/oval shape. Type AB has features of type A admixed with foci rich in lymphocytes. Type B1 resembles normal functional thymus, B2 has scattered plump cells with vesicular nuclei among a heavy population of lymphocytes, type B3 is predominantly composed of round or polygonal shape with minimal atypia, and type C is a thymic carcinoma with atypia with cytoarchitectural features no longer specific to the thymus. Modified Masaoka stage IIIA involves macroscopic invasion of neighboring orangs such as pericardium, and lung without invasion of great vessels, whereas IIIB has invasion of great vessels. References: Masaoka, A., J Thorac Oncol, October 2010, Vol 5, number 10, Suppl 4, S304-S312.; Kondo et al., Ann Thorac Surg, 2004, 77; 1183-1188.; Wright CD., Critc Rev Oncl Hematol, 2008, 65: 109-120.

Question 20

What is a major safety risk of information technology systems in radiation oncology?

Answer 20

Loss of data

= Rationale: Failover protection and file archiving are used to mitigate impact if a system fails. DICOM transfers are standard actions and do not pose major safety risks.

Question 21

Which soft tissue sarcoma subtype has a better DSS than other subtypes, but a higher local relapse rate?

Answer 21

Myxofibrosarcoma

= Rationale: In multiple institutional series, myxofibrosarcoma has demonstrated a better disease-specific survival than other sarcoma subtypes, but also a higher local relapse rate. Propensity for local recurrence is predicted by positive or close margins at resection. Aggressive surgery combined with radiotherapy may contribute to more effective local control.

Question 22

A recent pooled analysis of two Phase-III studies (STARS and ROSEL) examining SABR/SBRT versus surgery for early stage NSCLC demonstrated:

Answer 22

a statistically superior OS in favor of the radiation arm.

= Rationale: Estimated overall survival at 3 years was 95% in the SABR group compared with 79% in the surgery group (p=0·037). Recurrence-free survival at 3 years was 86% in the SABR group and 80% in the surgery group (p=0·54). Grade 3-4 toxicity rates were 44% in the surgery arm versus 10% in the SABR arm. References: Chang JY. Lancet Oncology, 2015 Jun, 16(6):630-7.

Question 23

What molecular marker provides prognostic information for grade II astrocytomas?

Answer 23

IDH

= Rationale: Gliomas are classified by molecular status in view of data identifying molecular markers such as isocitrate dehydrogenase (IDH), to be predictive of clinical outcome. IDH mutation is associated with more favorable outcomes.

Question 24

For the commissioning of a new LINAC, what is a 3D, scanning water tank system used to measure?

Answer 24

Beam profiles

= Rationale: Option B is incorrect because the water tank would get in the way of measurements of output versus gantry angle. Option C is incorrect because in air measurements are taken without a water tank. Option D is incorrect because head leakage is measured in air and at the linac-specific location of highest leakage.

Question 25

            In an epidemiologic study, 500 workers with respiratory disease and 200 workers without respiratory disease were studied. Of those with disease, 250 reported exposure while only 50 without disease reported being exposed. This study is best described as a:

Answer 25

            case-control study. = Rationale: A case-control study looks backward in time to detect a cause to a particular outcome. A cohort study occurs over extended time to study a characteristic suspected of being a precursor to the effect and tries to answer what will happen. A cross-sectional study is a snapshot of what is happening at the moment. A randomized clinical trial looks at the result relative to the intervention.

Question 26

            Regarding EORTC 22845, which randomized patients with low grade glioma to 54 Gy vs. observation, what outcome was improved by the use of early radiation therapy?

Answer 26

            Progression free survival = Rationale: The EORTC 22845 trial randomized patients to 54 Gy vs observation. The median progression free survival was statistically different, 5.3years vs 3.4years and the 5 year PFS was 55% vs 35%. However the median overall survival was not statistically different at 7.4 years vs 7.2 years.

Question 27

            Which of the following isotopes is used for single photon emission computed tomography (SPECT)?

Answer 27

            99mTc = Rationale: 99mTc is used in ~85% of nuclear medicine procedures. It satisfies many requirements for an injectable imaging radioisotope (emits a well-defined and highly detectable 140.5 keV gamma, has short physical and biological half-lives, can be produced with high specific activity, it is easy to use and store, etc.). 18F emits primarily positrons rather than photons, making is useful for positron emission tomography. 82Rb is also a positron emitter, albeit less common than 18F. 60Co is useful for teletherapy as it emits high energy gamma photons with a very long half-life, but as such is not suitable for injection or SPECT applications.

Question 28

            What spinal cord dose results in a 50% risk of myelopathy?

Answer 28

            69 Gy = Rationale: 69 Gy has a 50% risk of myelopathy.

Question 29

            The tumor PD-L1 expression enrollment requirement in the KEYNOTE-024 Phase-III randomized study for untreated advanced NSCLC (pembrolizumab vs chemotherapy) was:

Answer 29

            50%. = Rationale: To be eligible for the Keynote-010 study, patients with previously treated advanced NSCLC were required to have at least 1% tumor cells with PD-L1 expression. In the total patient population, median OS in the two pembrolizumab dose arms was significantly longer than docetaxel. In a planned subset analysis of patients with expression of PD-L1 on 50% of the tumor cells, median OS and PFS in the two pembrolizumab dose arms was significantly longer than docetaxel.

Question 30

            What site of localized Ewing Sarcoma is most likely to be treated with radiation alone?

Answer 30

            S1 vertebral body = Rationale: In Ewing Sarcoma, the local therapy decisions are made by the radiation oncologist, surgeon, medical oncologist, and family based on feasibility and morbidity of surgery. “Expendable” or “dispensable” bones—such as the fibula, clavicle, ribs, or some bones of hand/feet—are very likely to be treated with surgery because the long-term morbidity of resection of these bones considered reasonable. Pelvic and sacral lesions, particularly those involving sacral nerve roots, are much more difficult surgeries and the surgeries can be very morbid.

Question 31

            In treating vulvar cancer with an involved pelvic lymph node, the superior field border can be raised what distance above the most cephalad-positive node?

Answer 31

            5 cm = Rationale: The superior border should be no lower than the bottom of the sacroiliac joints or higher than L4/L5 junction unless the pelvic LNs are involved. If the pelvic LNs are involved the upper border can be raised to 5cm above the most cephalad-positive node.

Question 32

            Receiver Operating Characteristic (ROC) curve is a plot of the true positive rate against the false positive rate for the different possible cut points of a diagnostic test. Which of ROC curve demonstrates the best test accuracy?

Answer 32

Little "r" shape = Rationale: The area under the ROC is a measure of test accuracy. The closer the curve follows the left-hand border and then the top border of the ROC space, the more accurate the test. The closer the curve comes to the 45-degree diagonal of the ROC space, the less accurate the test.

Question 33

            In patients with Mycosis Fungoides who receive total skin electron beam therapy (TSEBT), a boost is required to which area?

Answer 33

            Scalp = Rationale: The scalp, perineum, and soles of the feet require a boost because they involve body surfaces that are tangential to the TSEBT beam axis and therefore otherwise do not receive sufficient dose. The elbows, hands, and neck are adequately exposed and therefore do not require a boost. References: Chen Z, et al., Int J Radiat Oncol Biol Phys, 2004 Jul 1, 872-85.

Question 34

            Compared to patients who received temozolomide alone, what was the cognitive function and health-related QoL at 3 years for patients who received radiation alone on EORTC 22033-26033 for high risk, low grade glioma?

Answer 34

            Similar cognitive function, similar QoL = Rationale: The EORTC 22033-26033 study for high risk low grade gliomas randomized patients to either 50.4Gy versus temozolomide for up to 12 cycles. In their report of health-related quality of life and mini-mental status exam (MMSE), the analysis showed no significant differences between the groups for change in MMSE scores during 3 years of follow up for patients receiving radiation versus 1 year of temozolomide.

Question 35

            How did the addition of WBRT affect outcomes in the NCCTG N0574 randomized trial of SRS alone vs. SRS WBRT for treatment of brain metastases?

Answer 35

            Similar OS, worse cognitive function = Rationale: Patients treated with SRS alone had less cognitive deterioration at 3 months compared to patients treated with SRS + WBRT. The median OS of patients treated with SRS + WBRT was 7.4 months vs. 10.4 months for SRS alone (HR, 1.02; 95% CI, 0.75-1.38; p = .92).

Question 36

            In patients with thymoma, the preferred choice of chemotherapy regimen for patients with unresectable disease is:

Answer 36

            cisplatin, doxorubicin and cyclophosphamide = Rationale: For locally advanced thymomas, induction chemotherapy with cisplatin, doxorubicin and cyclophosphamide (CAP) or CAP + prednisone is recommended with an overall response rate of 70% or more (Kim et al, Lung Cancer 2004). The alternate approach is induction chemoRT with CAP chemotherapy plus thoracic radiation therapy with a reported overall response rate of nearly 70% (Loehrer PJ Sr et al. JCO 1997).The preferred chemotherapy regimen for thymic carcinoma is carboplatin and paclitaxel. Other regimens are not recommended as first line therapy.

Question 37

            Vaginal tumors are BEST visualized using MRI:

Answer 37

            T2 images with vaginal gel. = Rationale: Vaginal tumors generally are best seen on MRI using T2 images with vaginal gel inserted into the canal which distends the vaginal walls and aids in assessing the tumor’s thickness.

Question 38

            According to GEC ESTRO recommendations for 3D image-based treatment planning for cervical cancer brachytherapy, which volume is used to assess high dose regions?

Answer 38

            V150 = Rationale: Cumulative DVH are recommended for evaluation of complex dose heterogeneity. DVH parameters for GTV, HR CTV and IR CTV are the minimum dose delivered to the 90% and 100% of the respective volume: D90 and D100. The volume, which is enclosed by the 150% and 200% of the prescribed dose (V150 and V200) is recommended for overall assessment of high dose volumes.

Question 39

            What describes beta-minus nuclear decay?

Answer 39

            A neutron becomes a proton, creating an electron and antineutrino = Rationale: Beta-minus or negatron decay occurs when there is an excess of neutrons in the atomic nucleus. To achieve greater stability, a neutron transforms into a proton, thereby bringing the neutron/proton ratio closer to the line of stability. To conserve charge, a negatron (electron) is created. To conserve spin/angular momentum, an antineutrino is created. The decay energy is imparted as kinetic energy split between the negatron and antineutrino. References: Khan FM. The Physics of Radiation Therapy. Lippincott Williams and Wilkins. 2003, 3rd Ed., p. 20-21.

Question 40

            Two nuclei are isomers if they have:

Answer 40

            the same number of neutrons and protons but different energy states. = Rationale: This is based on the definition of an isomer. When two nuclei have the same number of nucleons they are referred to as isobars. When two nuclei have the same number of protons but a different number of neutrons they are referred to as isotopes.

Question 41

            What minimum radiation dose to the whole volume of both kidneys will likely result in nephropathy with hypertension and anemia?

Answer 41

            30 Gy in 2 Gy/Fx = Rationale: The kidneys are radiosensitive late responding tissues. Radiation damage develops slowly, reflective of the slow turnover of the tissue. Radiation nephropathy usually manifests as proteinuria and hypertension, with anemia. The fractionation sensitivity of the kidney is high (i.e. the ?/? ratio is low). The dose tolerated by the kidney does not increase with increasing time after radiotherapy, but declines because of a continuous progression of damage, after doses well below the threshold for induction of functional deficit, which usually precludes re-irradiation. The pathogenesis of radiation nephropathy is complex. Most studies suggest glomerular endothelial injury as the start of a cascade leading to glomerular sclerosis and later tubulo-interstitial fibrosis. Several experimental studies have shown the importance of the renin–angiotensin system in the induction of glomerular sclerosis via upregulation of plasminogen activator inhibitor 1 (PAI-1) and enhanced fibrin deposition. Owing to loss of tubular epithelial cells, fibrin may then leak into the interstitium causing the onset of tubulointerstitial fibrosis. One or partial kidney irradiation can receive higher doses before damage is evident, but the whole bilateral volume is irradiated a dose of 30 Gy is sufficient to produce damage.

Question 42

            Which factor is linked with radiation induced pneumonitis?

Answer 42

            Transforming growth factor-?1 (TGF-?1) = Rationale: Transforming growth factor beta 1(TGF-?1) gene controls proliferation and cellular differentiation. TGF-?1 is an important modulator of the inflammatory response and in the development of tissue fibrosis in irradiated lungs. Animal and human studies have demonstrated that TGF-?1 is a major regulator of radiation-induced lung injury. Administration of anti-TGF-?1 antibodies can decrease the inflammatory response and reduce TGF-?1 activation several weeks after radiotherapy.

Question 43

            Determine the median value for the following data set: (23, 12, 77, 59, 31, 47, 48)

Answer 43

            47 = Rationale: The middle value = median = 47

Question 44

            In ASCENDE-RT randomized trial comparing 3DCRT boost vs. LDR I-125 boost after 46 Gy whole pelvic EBRT, brachytherapy boost was associated with:

Answer 44

            improved biochemical PFS. = Rationale: In ASCENDE-RT trial, brachytherapy boost was associated improved biochemical PFS but worse urinary toxicity.

Question 45

            Ovoid positioning was evaluated for the cervical cancer trials RTOG 0116 and 0128. What is the impact on LR and DFS if the ovoids are displaced away from the OS?

Answer 45

            Increase, decrease = Rationale: Patients with displacement of ovoids in relation to the cervical os have a significantly increased risk of local recurrence with decreased DFS as evaluated in RTOG 0116 and 0128.

Question 46

            In INT-0091, what was the 5 year incidence of isolated local failure in pediatric patients with Ewing Sarcoma treated with radiation alone for local control?

Answer 46

            9% = Rationale: The 5-year incidences of isolated local failure with radiation alone, surgery alone, combination surgery and radiation were 9.2%, 5.1% and 2%, respectively. However, this was not statistically significant. Moreover, the local control decision was not specified by the protocol, so there is speculation that there was an adverse selection for the patients treated with radiation alone. Further, the selection of local therapy modality does not appear to affect event free survival as even patients with localized disease are most at risk of metastatic recurrences.

Question 47

            Based on the updated results of Intergroup 0116 trial, which subset of patients with resected gastric cancer is unlikely to benefit from adjuvant chemoRT?

Answer 47

            Diffuse histology = Rationale: Updated analysis of the INT 0116 trial (Smalley S, J Clin Oncol 2012) showed a benefit to adjuvant chemoradiation for most subsets, with the notable exception of patients with diffuse histology. References: Smalley S, J Clin Oncol 2012

Question 48

            According to the International Consensus Contouring Guidelines for Adjuvant Radiation for Bladder Cancer, the superior anatomic border of the cystectomy bed CTV should extend 2 cm superior to the:

Answer 48

            superior aspect of the pubic symphysis . = Rationale: The superior anatomic border of the contour will extend 2 cm superior to the superior aspect of the pubic symphysis.

Question 49

            Regarding the IELSG (International Extranodal Lymphoma Study Group) 10 Phase II trial for DLBCL of the testes, what was the dose to the contralateral testes DLBCL?

Answer 49

            30 Gy = Rationale: The IELSG-10 phase II included 53 patients from age 22- with stage I or stage 2 Primary DLBCL of the testes. They were treated with 6 cycles of R-CHOP every 21 days with 4 doses of IT MTX and RT to contralateral testes (30 Gy) and to regional LNs (30-36) for stage II disease. 5 yr PFS was 74% and OS was 85%; There were no deaths as result of toxicity. Testicular RT was associated with good outcome and avoided contralateral testis relapse. References: Vitolo U et al., JCO, 2011 July 10, 2766-72; 29(20).

Question 50

            How were the target volumes defined on the RTOG 0630 trial of pre-operative radiation and daily image guidance for extremity soft tissue sarcoma?

Answer 50

            GTV was defined by use of T1 weighted gadolinium enhanced MRI = Rationale: On RTOG 0630 trial of pre-operative radiation for soft tissue sarcoma of the extremity with daily image guidance, target volumes were defined as follows: GTV was defined by MRI T1 plus contrast images. Co-registration of pretreatment MRI and planning CT in the same position was recommended to delineate the GTV for RT planning. For intermediate to high-grade tumors >= 8 cm, CTV=GTV +3 cm margins in the longitudinal (proximal and distal) directions. The radial margin was 1.5 cm beyond the GTV. For low-grade tumors or < 8 cm, the longitudinal margin was 2 cm beyond the GTV and, the radial margin was 1 cm. The CTV was expanded to cover the suspicious edema if it extended beyond the CTV margin and was constrained by anatomic barriers, including fascia, bone, or compartment. PTV included CTV plus 5 mm for all patients.

Question 51

            The spinal cord maximum dose constraint when planning definitive twice-daily radiotherapy for patients with limited-stage SCLC with modern radiation techniques is:

Answer 51

            41 Gy. = Rationale: Based on the CALGB 30610/RTOG 0538 protocol, the max dose constraint on the spinal cord for patients receiving definitive chemoradiation to 45 Gy in 30 fractions BID should not exceed 41 Gy. References: CALGB/RTOG 0538 study, CALBG/RTOG protocol. NCCN 2017.

Question 52

            What percentage of oropharyngeal cancers in the United States are currently caused by HPV?

Answer 52

            >60% = Rationale: Human papillomavirus (HPV) causes an epidemiologically and clinically distinct form of oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive OPSCCs have risk factors related to sexual behavior whereas HPV-negative cancers are strongly associated with tobacco and alcohol use. HPV is now the major cause of oropharyngeal cancer in the United States. The incidence has increased significantly over the last 20 years. References: Chaturvedi AK, Engels EA, Pfeiffer RM, et al., Human papillomavirus and rising oropharyngeal cancer incidence in the United States, Journal of Clinical Oncology 2011; 29(32):4294–4301.

Question 53

            Which circular electron beam field will result in the lowest relative surface dose?

Answer 53

            6 MeV, 8 cm diameter = Rationale: For electron beams, relative dose at the surface increases with beam energy. This occurs because lateral scatter reduces with increases in energy. With reduced scatter, electron fluence becomes increasingly similar between shallow regions and the depth of maximum dose (or, said differently, the relative depth-dose ratio approaches unity as incident beam energy is increased). Additionally, loss of lateral charged particle equilibrium results in increased surface dose and decreased depth of maximum dose. A rule-of-thumb for central axis equilibrium is that the field radius Req in [cm] should satisfy Req ? 0.88*?(E). For 6 MeV this is 2.2 cm, and for 18 MeV is 3.7 cm. Thus, option B (low energy, large field) will have the lowest relative surface dose.

Question 54

            What factor is included in the Gail model for predicting risk of developing breast cancer?

Answer 54

            Number of prior breast biopsies = Rationale: The Gail model was one of the initial tools that attempted to estimate a woman’s risk of developing breast cancer over the next 5 years. It considers age, race, age of first menstrual period, number of first degree relatives with a history of breast cancer, and number of prior biopsies. It is thought to underestimate the need for testing as it does not take into consideration a family history of ovarian cancer, age of onset of breast cancer, occurrence of bilateral breast cancers, history of second degree relatives with breast cancers, or the biology of the breast cancer; all important in assessing risk.

Question 55

            Which dose quantity is used to assess the radiation exposure to radiation workers?

Answer 55

            Effective dose equivalent = Rationale: Radiation workers are limited to an annual effective dose equivalent of 50mSv. The effective dose equivalent is used since it takes into account differences in radiation type, tissue sensitivity, and internal/external exposure.

Question 56

            For treatment of liver metastases with SBRT, what is the liver dose constraint for a 3-5 fraction regimen?

Answer 56

            700 cc of liver should receive < 21 Gy = Rationale: Eligible patients had one to five hepatic metastases, ability to spare a critical hepatic volume (volume receiving <21 Gy) of 700 ml, adequate baseline hepatic function, no concurrent antineoplastic therapy, and a Karnofsky performance score of ?60. There was no grade 4 or 5 toxicity or treatment-related grade 3 toxicity. References: Rule W. Phase I dose-escalation study of stereotactic body radiotherapy in patients with hepatic metastases. 2011 Apr. 18(4):1081-7.

Question 57

            Per PORTEC-2 (Postoperative Radiation Therapy in Endometrial Carcinoma), what is the same for EBRT and vaginal brachytherapy?

Answer 57

            Vaginal cuff recurrence = Rationale: PORTEC-2 was a randomized study that compared adjuvant external beam radiotherapy to vaginal cuff brachytherapy for patients with intermediate-risk endometrioid adenocarcinomas. While pelvic relapses were more frequent in the brachytherapy arm, vaginal recurrence rates were comparably low in both arms. The toxicity measures strongly favored brachytherapy.

Question 58

            For patients with limited stage SCLC who receive first cycle of chemotherapy prior to the start of radiation, the nodal target volume should cover:

Answer 58

            initially involved nodal region but post-induction volume. = Rationale: While historical nodal irradiation volumes for patients with limited stage- SCLC have extended to beyond involved nodal regions, modern series and clinical trials omit elective nodal irradiation (ENI). Further, a small randomized study reported by Hu et al., observed that irradiation of post-chemotherapy tumor extent without ENI did not have a negative impact on loco-regional control. Hence, for patients who start systemic therapy prior to the radiation therapy, the current NCCN guidelines recommend irradiation of the involved nodal region but using post-induction volume.

Question 59

            What was the conclusion from the secondary analysis of RTOG 0617 randomized clinical trial evaluating the radiation dose (60 Gy vs 74 Gy) for NSCLC?

Answer 59

            Lower grade ?3 pneumonitis was seen with IMRT = Rationale: In the secondary analysis of RTOG 0617 data, the use of IMRT was associated with reduced rates of ? grade 3 pneumonitis (7.9% vs 3.5%, p = 0.039), reduced dose to heart without any differences in 2-year OS, PFS, local or distant failure despite having larger PTV: Volume of lung ratio. Lung V20 Gy and not V5 Gy was associated with increased ? grade 3 pneumonitis. Hart V40 Gy was associated with OS. References: Chun et al. J Clin Oncol, 2017 Jan, 35(1):56-62.

Question 60

            In the 8th edition of the AJCC Staging system, oral cavity T-category will now include which of the following?

Answer 60

            Depth of invasion = Rationale: The AJCC 8th edition incorporates depth of invasion (DOI) in assigning a T-category for oral cavity cancer. This recognizes the prognostic importance of a deeply invasive tumor, even if it is a small tumor. Previous staging did not include depth of invasion.

Question 61

            The tumor PD-L1 expression enrollment requirement in the KEYNOTE-010 phase 2/3 randomized study for previously treated advanced NSCLC (pembrolizumab vs docetaxel) was:

Answer 61

            1%. = Rationale: To be eligible for the Keynote-010 study, patients with previously treated advanced NSCLC were required to have at least 1% tumor cells with PD-L1 expression. In the total patient population, median OS in the two pembrolizumab dose arms was significantly longer than docetaxel. In a planned subset analysis of patients with expression of PD-L1 on 50% of the tumor cells, median OS and PFS in the two pembrolizumab dose arms was significantly longer than docetaxel.

Question 62

            In patients with T1-T2 invasive breast cancer with 1 to 3 positive axillary nodes, what are the effects of postmastectomy radiation?

Answer 62

            Decreases LRF, decreases breast cancer mortality = Rationale: PMRT decreases the risk of locoregional failure, any recurrence, and also decreases breast cancer mortality. The benefit of PMRT has to be weighed against potential toxicities associated with radiation therapy. References: Recht et al., Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update, 2016; Practical Radiation Oncology. Vol 6, issue 6, 219-234.

Question 63

            In a meta-analysis of randomized trials (Auperin et al., JCO 2010), the use of concurrent chemoRT (versus sequential chemoRT) in patients with locally advanced NSCLC demonstrated:

Answer 63

            improved LC and OS, but not DM . = Rationale: Concurrent chemoRT increased OS by 4.5% at 5 years (p=0.004), and decreased locoregional progression (HR 0.77 (p= 0.01). No effect (HR of 1.04) was noted on distant progression. Grade 3-4 esophagitis increased from 4% to 18% with a HR of 4.9.

Question 64

            In which part of the radiation damage response does DNA-dependent protein kinase (DNA-PKcs) primarily function?

Answer 64

            Non-homologous end joining repair = Rationale: There are two major types of DSB repair pathways in mammalian cells – homologous recombination repair (HRR) and non-homologous end-joining (NHEJ). A third type, single-strand annealing (SSA), shares components with both NHEJ and HRR. NHEJ uses little to no sequence homology in a process that may or may not be error-free. NHEJ requires fewer proteins than HRR, The NEHL proteins are Ku70/80, DNA-PKcs, DNA ligase IV, and XRCC4. HRR is dependent on DNA homology and is error-free. The requirement for sequence homology is the fundamental difference between HRR and NHEJ. It is generally believed that NHEJ plays a more important role than HRR in mitotically replicating cells while HRR may play a more prominent role when sister chromatids are available during late S and G2 stages of the cell cycle. NHEJ is more important during G1 and early S phase, while HRR operates in S and G2 due to the requirement for sequence homology.

Question 65

            In a patient, electrons lose energy predominantly through:

Answer 65

            inelastic collisions with atomic electrons = Rationale: In water or tissues, electrons lose energy predominately through inelastic collisions (ionization and excitation) with atomic electrons.

Question 66

            What were the preliminary 1 year toxicity results of RTOG 1014 trial of partial breast re-irradiation following second breast conserving surgery for recurrent breast cancer after previous breast conservation?

Answer 66

            <5% rate of grade 3 fibrosis = Rationale: RTOG trial 1014 evaluated partial breast re-irraditation after second lumpectomy in patients previously treated with breast conservation. A protracted hyperfractionated course of treatment was used (45 Gy in 30 fractions given bid). Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 (<2%) grade >= 3 and identified as grade 3 fibrosis of deep connective tissue.

Question 67

            Which HPV strain is MOST commonly associated with oropharyngeal cancer?

Answer 67

            HPV 16 = Rationale: In the oropharynx, HPV 16 accounts for more than 90% of all HPV-associated cancers.

Question 68

            A recent multi-institutional analysis of brain metastases from EGFR-mutant NSCLC which examined sequencing of SRS, WBRT, and EGFR-TKI therapy, demonstrated:

Answer 68

            SRS followed by EGFR-TKI resulted in the longest OS. = Rationale: The median OS for the SRS, WBRT, and EGFR-TKI cohorts was 46, 30, and 25 months, respectively. Upfront SRS had the best survival outcomes with improved survival in both favorable and unfavorable patient groups, when stratified by ds-GPA. Despite having more patients with less favorable prognosis, even on multivariate analysis upfront WBRT had improved survival over upfront EGFR-TKI (30 vs 25 months, median OS, p < 0.039). Deferring RT was associated with inferior OS.

Question 69

            During a patient-specific IMRT QA validation, a Gamma Index pass rate of 92% means:

Answer 69

            92% of points evaluated have a gamma value of 1 or less. = Rationale: When using the gamma criterion, the gamma value of each point is calculated, and the point is considered to pass the test if the gamma value is 1 or less.

Question 70

            An HDR plan was created using a source activity before a source exchange, but it will be delivered after a source exchange. What MUST be adjusted in the plan to deliver the intended dose?

Answer 70

            Decrease the source dwell times = Rationale: The dose scales with the source activity and dwell times. With a higher activity source, to deliver the same total dose with the same dose distribution as the plan, but with a higher activity source, the dwell times must be reduced. If the step sizes changed, the dose distribution would change.

Question 71

            In a randomized Phase III trial (DART 01/05) using 78 Gy for prostate cancer, long-term androgen deprivation (24 months), when compared with short term androgen deprivation (4 months), was associated with a higher risk of:

Answer 71

            cardiovascular events. = Rationale: In DART 01/05 randomized trial, LTAD did not significantly impact urinary or rectal radiation-induced toxicity but was associated with a higher risk of cardiovascular events.

Question 72

            A clinical T1N0 larynx cancer does NOT require nodal treatment when it originates at which subsite?

Answer 72

            True vocal cord = Rationale: Less than 5% of patients with clinical T1 disease confined to the glottic larynx have involved lymph nodes. Therefore, the traditional small-field to treat an early-stage glottic larynx cancer does not include lymph nodes.

Question 73

            In a secondary analysis of the KEYNOTE-001 study, use of previous radiotherapy for patients with NSCLC receiving pembrolizumab:

Answer 73

            improved PFS and OS. = Rationale: In patients who previously received any radiotherapy than in patients without previous radiotherapy use of pembrolizumab was associated with longer PFS (hazard ratio [HR] 0·56 [95% CI 0·34-0·91], p=0·019; median progression-free survival 4·4 months [95% CI 2·1-8·6] vs 2·1 months [1·6-2·3]) and longer OS (HR 0·58 [95% CI 0·36-0·94], p=0·026; median overall survival 10·7 months [95% CI 6·5-18·9] vs 5·3 months [2·7-7·7]). Grade ? 3 pulmonary toxicity with or without thoracic RT was similar (17% vs 12%). Any pulmonary toxicity was 63% vs 40% (p = 0.058). Differences in anemia or esophagitis were not reported. References: Shaverdian et al. Lancet Oncol, 2017 Jul, p. 18(7):895-903.

Question 74

            Which chemotherapeutic agents is correctly paired with its target?

Answer 74

            5- fluorouracil - thymidylate synthase = Rationale: 5- fluorouracil targets thymidylate synthase. Topotecan targets topoisomerase I, bevaciuzmab targets VEFG, and sunitib is a tyrosine kinase inhibitor which targets EFGF, VEGFR, KIT, and EGFR.

Question 75

            According to SWOG S0809, which adjuvant treatment has been established as standard-of-care for resected extrahepatic cholangiocarcinoma and gallbladder cancers?

Answer 75

            Gemcitabine+capecitabine followed by capecitabine+RT = Rationale: The trial was a phase II prospective trial of patients with resected gallbladder and extrahepatic cholangiocarcinomas (pT2-4 or N+ or positive margins, M0, performance status 0-1). Patients received gemcitabine+capecitabine followed by chemoradiation with capecitabine and RT to 54-59.4 Gy. The treatment was well-tolerated and median overall survival was 35 months, which was considered promising. This was the first multi-institutional prospective study of this disease.

Question 76

            What is the 5 year survival after laryngectomy for T4a laryngeal SCC?

Answer 76

            50% = Rationale: T4a laryngeal cancer treated with laryngectomy has a 5 year survival of around 50% across multiple reports. A review of published reports showed an average survival of 46%. Laryngeal preservation in these patients has a lower overall survival and is not recommended in guidelines.

Question 77

            According to PORTEC-1, which outcome is associated with adjuvant EBRT over observation?

Answer 77

            Increased incontinence for urine = Rationale: PORTEC-1 was a randomized study that compared adjuvant external beam radiotherapy to observation for select endometrioid adenocarcinomas. While local control was improved in the EBRT arm, long term follow up shows no improvement of survival by EBRT. Toxicity outcomes for EBRT are markedly worse. References: Nout RA, J Clin Oncol, 2011 May 1, 29(13):1692-700.

Question 78

            According to consensus guidelines, which nodal regions should be included in the CTV for preoperative treatment of gastroesophageal junction adenocarcinoma?

Answer 78

            Gastrohepatic and celiac nodes = Rationale: Consensus contouring guidelines (Wu A et al., Int J Radiat Oncol Biol Phys 2015; 92:911-920) recommend routinely including the gastrohepatic nodes, which are among the most commonly involved nodes in GE junction and distal esophageal cancer. Though the rate of celiac nodes is somewhat lower, routine inclusion was recommended by the consensus panel. Superior mesenteric nodes are not considered regional nodes in esophageal cancer and are not recommended to be included routinely in the CTV. References: Wu A et al., Int J Radiat Oncol Biol Phys 2015; 92:911-920.

Question 79

            With a median follow-up of 12 years, the addition of 24 months of anti-androgen therapy (peripheral androgen blockade) during and after salvage radiotherapy (RTOG 9601) significantly:

Answer 79

            B improved overall survival. = Rationale: With a median follow-up of 12 years, the addition of 24 months of anti-androgen therapy (peripheral androgen blockade) during and after salvage radiotherapy (RTOG 9601) significantly improved overall survival (76.3%) bicalutamide group) vs 71.3% (placebo group), reduced metastatic prostate cancer, reduced death from prostate cancer, reduced local recurrence and tumor progression and no difference in toxicity.

Question 80

            Which key kinase regulator links the initial recognition of DNA double strand breaks with signaling for cell cycle arrest and break repair?

Answer 80

            ATM = Rationale: The ataxia-telangiectasia-mutated (ATM) protein kinase is rapidly and specifically activated in response to DNA double-strand breaks in eukaryotic cells. MRN complex is required for ATM activation after double strand breaks (DSBs). Activated ATM then plays a role in cell cycle delay after DNA damage, especially after double-strand breaks (DSBs). ATM together with NBS1 act as primary DSB sensor proteins. These modified mediator proteins then amplify the DNA damage signal, and transduce the signals to downstream effectors such as CHK2 and p53.

Question 81

            In the COMS randomized trial of enucleation verses brachytherapy for medium choroidal melanomas, what percentage of patients developed blindness (visual acuity 20/200 or worse) in the treated eye 3 years after brachytherapy?

Answer 81

            45% = Rationale: In this trial, we learned that OS was not compromised by a globe-preservation approach, with very few local failures after brachytherapy (~10%). Visual acuity diminished to 20/200 or worse in the years after brachytherapy: 17% by 1 year, 33% by 2 years, 43% by 3 years.

Question 82

            In the Phase-I RTOG 0813 study that examined SBRT for centrally located NSCLC treated in 5 fractions:

Answer 82

            the 2-year LC at the two highest dose-cohorts was 85-90%. = Rationale: Medically inoperable patients, predominantly elderly, were included in the study. The MTD in the phase I data was 12Gy/fr x 5 fractions. The 2-year local control rates for the two highest cohorts (11.5 Gy and 12 Gy) were 89.4% (90% CI: 81.6-97.4%) and 87.7% (90% CI: 78.3-97%), respectively. Grade 5 toxicity attributed to SBRT was seen in 3 out of 71 patients treated at these two cohorts. T1-2 (< 5 cm) tumors were treated on this study. References: Bezjak A. et al., IJROBP, October 1, 2016, p. 96(2):S8.

Question 83

            What is included in the FLIPI Score (Follicular Lymphoma International Prognostic Index)?

Answer 83

            Hemoglobin = Rationale: FLIPI is a prognostic score that was developed from large retrospective data from patients with follicular lymphoma, and includes Age > 60, Ann Arbor Stage III/IV, number of nodal sites > 4, hemoglobin, and serum LDH. Based on number of risk factors, 5 yr OS can range from 52.5% to 91% (in the pre-rituxan era); This can be used to improve treatment choices and to compare clinical trials.

Question 84

            In the CROSS trial of preoperative chemoRT vs. surgery alone for esophageal cancer, what was the approximate rate of locoregional recurrence in the chemoRT arm?\

Answer 84

            15% = Rationale: Analysis of patterns of recurrence in the CROSS trial (Oppedijk V et al, J Clin Oncol ’14) showed that the rate of locoregional recurrence was reduced from 34% to 14% with the use of preoperative chemoradiation. (p<0.001).

Question 85

            What is the shape of the excess relative risk dose response for solid tumors in females from the Life Span study of atomic bomb survivors?

Answer 85

            Linear with no threshold = Rationale: The most recent results from the Life Span study of atomic bomb survivors (1958-2009) indicates a linear dose response for excess relative risk of solid tumor formation in females. This response has no threshold. Contrary to previous results, the male data was best fit by a linear-quadratic model also with no threshold. The Radiation Effects Research Foundation (RERF) is being cautious about inferring what this result means and has adapted a conservative approach with regard to setting radiation safety limits. They believe that further study is necessary before making any changes to currently accepted standards.

Question 86

            How does the sensitivity of proton beams to tissue heterogeneities compare to that of photon beams?

Answer 86

            More sensitive = Rationale: Proton beams are more sensitive to tissue heterogeneities because small changes to density will have a large impact on the dose due to the final location of the Bragg Peak. References: Dieterich. Practical Medical Physics. Elsevier. 2015, 1st Ed., p. 132.

Question 87

            Higher prevalence of basal-like breast cancer is associated with which risk factors or patient subgroups?

Answer 87

            Premenopausal African American women = Rationale: Basal-like breast tumors occurred at a higher prevalence among premenopausal African American patients compared with postmenopausal African American and non-African American patients in this population-based study. Breast feeding was associated with reduced risk of basal like breast cancer. Obesity with associated with increased risk of basal-like breast cancer in pre- and postmenopausal women. References: Carey, LA et. al., JAMA. 2006; 295(21): 2492.

Question 88

            For treatment of primary CNS lymphoma, what is the minimum dose of methotrexate needed to cross the blood-brain barrier?

Answer 88

            3.0 g/m2 = Rationale: Doses above 3.0 to 3.5 g/m2 are enough to cross the blood brain barrier.

Question 89

            Based on NCRP, what is the total dose limit for the fetus of a pregnant radiation worker?

Answer 89

            5 mSv = Rationale: According to the guidelines of the NCRP Report No.91, the fetus can receive a maximum of 5 mSv over the whole course of pregnancy.

Question 90

            Which change has been incorporated into the AJCC Staging 8th edition for breast cancer?

Answer 90

            Multigene recurrence score = Rationale: There are many changes to breast cancer staging in the AJCC 8th edition including anatomic stage group and prognostic stage group, incorporation of biomarkers such as ER/PR/Her2 status, grade, and recurrence scores. Lobular carcinoma in situ (LCIS) has been removed from AJCC breast staging and is no longer Tis as it is treated as a benign entity. Breast sarcomas, phyllodes tumors, and breast lymphomas are not included in the breast cancer staging system. Tumor markers are not included in the staging system.

Question 91

            Which en-face electron beam energy is preferable to spare an organ at risk (OAR) at a depth of 5 cm?

Answer 91

            9 MeV = Rationale: The range of an electron beam is given by E/2. To spare something at a depth of 5 cm, only the 9 MeV beam works (range of 4.5 cm)

Question 92

            What does the term “uterine junctional zone” refer to in MRI imaging?

Answer 92

            Low T2 signal of the innermost myometrium = Rationale: Junctional zone is a distinct area of low (bright) T2 signal in the uterus on pelvic MRI. It has been histologically correlated to the inner myometrium (i.e. situated just deep to the endometrium). Careful examination of the junctional zone appearance is helpful in the evaluation of the inoperable endometrial cancer. Breach or interruption of the junctional zone differentiates between tumors confined to the endometrium and those invading the myometrium.

Question 93

            What is the MOST appropriate timing, dose and means of radiotherapy for a 4 mm unilateral retinoblastoma without extra-ocular extension?

Answer 93

            Consolidative plaque brachytherapy prescribed to 5mm to 36 Gy after systemic chemotherapy +/-other focal therapies = Rationale: Episcleral plaque brachytherapy is preferred for localized tumors without extraocular extension or vitreous seeding when other focal therapies (diode, laser, cryo) and chemotherapy have failed to cause complete regression of the primary mass.

Question 94

            In which phase of the cell cycle are cells most sensitive to hyperthermia-induced cell killing mechanisms?

Answer 94

            S = Rationale: Hyperthermia is most effective at killing S phase cells, while S phase cells are most resistance to radiation-induced cell killing. Hyperthermia is most effective radiosensitizer if given at the time of radiation. However, the best therapeutic effective is achieved using sequential heat treatment rather than simultaneous treatment. Sequential treatment spares normal tissue injury because of differences in blood flow between tumor and normal tissues.

Question 95

            For a parallel-opposed, open field tangential breast plan, the lateral jaw is increased by 5cm to enhance the beam flash. What is the expected effect on the beam MUs?

Answer 95

            Decrease by ~3% = Rationale: As the field size is increased, the total scatter factor increases and the MUs will decrease for a fixed dose at depth. The change in total scatter factor from a 10x10 to a 30x30 field is less than 8% so a decrease of 10% is not likely.

Question 96

            Which side effect is associated with improved OS in patients receiving RT and cetuximab for head and neck cancer?

Answer 96

            Acneiform rash = Rationale: In a landmark phase III trial, patients with head and neck cancer undergoing definitive treatment with concurrent radiation therapy and cetuximab, patients who developed a grade 2 or greater acneiform rash had an improved overall survival when compared to patients with either no rash or a grade 1 rash.

Question 97

            A patient presents with a 4 cm right neck mass, progressive left maxillary formication sensation, and left retro-orbital pain. Right neck FNA demonstrates nasopharyngeal carcinoma. PET-CT shows uptake in the right neck mass and nasopharynx, with no evidence of distant metastases. How is this patient staged? (The staging is the same per 7th and 8th editions)

Answer 97

            T4N1M0 = Rationale: T4 designation, based here on cranial nerve involvement, is not subdivided for NPC. The upper bound for N1 disease is 6 cm.

Question 98

            Which photon interaction is most probable in the patient when performing a MV portal image for pre-treatment patient alignment?

Answer 98

            Compton scattering = Rationale: For a megavoltage beam produced by a linear accelerator for portal imaging (e.g. 6 MV), Compton scattering is the most probable interaction. This beam energy is well above the atomic electron binding energies that are responsible for the photoelectric effect, and below that required to produce substantial pair production. Rayleigh or coherent scattering is a small component of all photon interactions in radiotherapy and becomes appreciable only for very low energy photons in high atomic number materials.

Question 99

            Which oncovirus is associated with the development of Kaposi’s Sarcoma?

Answer 99

            Human herpesvirus 8 = Rationale: The presence of human herpesvirus 8 or Kaposi’s sarcoma-associated herpesvirus (KSHV) is a primary and necessary factor in development of Kaposi’s sarcoma. KSHV is also associated with primary effusion lymphoma and multicentric Castleman’s disease. Epstein-Barr virus (EBV) or human herpesvirus 4 is associated with Burkitt’s lymphoma and nasopharyngeal carcinoma. Human T-lymphotropic virus is associated with adult T-cell leukemia.

Question 100

            A slowly proliferating tumor has an ?/? ratio of 1.5 Gy. Dose-limiting normal tissue has an ?/? ratio of 5 Gy. Which fractionation schedule would likely result in the highest therapeutic ratio?

Answer 100

            Hypofractionation = Rationale: A hypofractionated treatment regimen who result in the highest therapeutic ratio since the tumor (a/b ratio=1.5 Gy) would be spared at a greater rate than the dose-limited normal tissue (a/b ratio = 5 Gy). A split-course treatment would not be beneficial since the a/b ratio indicates there would be greater recovery in the tumor as compared to the normal tissue, and accelerated treatment would not be indicated since the tumor is relatively slow-growing (Tpot= 35 days).

Question 101

            A grade III glioma is histologically consistent with an astrocytoma and has 1p19q co-deletion and IDH mutation. How should this tumor be classified according to the 2016 WHO classification?

Answer 101

            Anaplastic oligodendroglioma = Rationale: In the 2016 WHO Classification of Brain Tumors, at times molecular type determines the diagnosis rather than classic histology on H&E. A histologic astrocytoma, but a molecular oligodendroglioma (with IDH mutation and 1p19q co-deletions), is an oligodendroglioma. Similarly, a histologic oligodendroglioma but without 1p19q co-deletion is not an oligodendroglioma, assuming the molecular testing is accurate. A glioblastoma (GBM) is not a grade III tumor.

Question 102

            What is the typical consolidation radiation dose for DLBCL after complete response to chemotherapy?

Answer 102

            30 Gy = Rationale: The recommended dose after consolidation for CR for DLBCL after chemotherapy is 30-36 Gy; For PR, it is 40-50 Gy; For primary treatment for refractory or non-candidates for chemotherapy, it is 40-55 Gy; References: Zelenetz et al. NCCN Guidelines Version 3, March 2017, NHODG-D 3 of 4.

Question 103

            What is the goal of neoadjuvant chemotherapy for patients with bilateral Wilms tumor?

Answer 103

            Permit partial nephrectomy = Rationale: Neoadjuvant chemotherapy is primarily utilized to permit a nephron sparing approach given that end stage renal failure may occur in as much as 12 % of cases and is thus a major source of morbidity in this population. Response based omission of whole lung irradiation is not a goal of AREN 0534. Flank radiation fields remain the same size regardless of response to neoadjuvant chemotherapy. Neoadjuvant chemotherapy has not been shown to more effectively reduce the risk of local, regional or distant recurrence relative to adjuvant chemotherapy. References: Ann Surg.; AREN 0534; Hamilton TE 2011 May; 253(5):1004-10.

Question 104

108. What is the contralateral lung dose constraint when using IMRT after extrapleural pneumonectomy?

Answer 104

            Mean lung dose <8.5 Gy = Rationale: In the early MDACC IMRT experience, fatal pulmonary death was seen in ~10% of patients. Risk of pulmonary related death with a V20 of >7% was 42-fold higher and mean lung dose (MLD) of >8.5 Gy was 8.6-fold. The authors concluded to keep V20 < 7% and MLD < 8.5 Gy.

Question 105

            On the COG protocol D9803 for patients with intermediate risk rhabdomyosarcoma, what factor was associated with an increased risk of local failure?

Answer 105

            Size > 5 cm = Rationale: Only size was associated with an increased risk of local failure. 5y local failure for tumors >= 5cm was 25% vs. 10% for tumors < 5 cm (p = 0.0004) Histology, nodal status, and site were not associated with an increased risk of local failure.

Question 106

            What is the appropriate adjuvant radiation after resection of a 4 cm favorable histology Wilms tumor that did not extend beyond the kidney, with tumor spill throughout the abdomen?

Answer 106

            Whole abdomen radiation to 10.5 Gy = Rationale: Patients with diffuse spill (or pre-operative rupture) have Stage III disease and require whole abdomen radiation therapy. The dose for whole abdomen radiation in patients with favorable histology is 10.5 Gy in 7 fractions. Patients with favorable histology Wilms tumor and Stage I or II disease do not require adjuvant radiation therapy. There are a number of scenarios in which flank radiation is indicated, such as Stage I Wilms with unfavorable histology. Whole abdomen to 19.5 Gy can be used in cases of diffuse peritoneal implants. References: Halperin, et al. Pediatric Radiation Oncology. 5th edition Lippincott Williams and Wilkins. 2011.

Question 107

            Immunotherapy has been shown to be potentially effective in:

Answer 107

            microsatellite unstable colon cancer. = Rationale: A phase II study of pembrolizumab 10 mg/m2 every 14 days for microsatellite stable and unstable colon cancer demonstrated an objective response rate of 0% vs. 40%, respectively. To date, there has been little reported response to immunotherapy drugs among pancreatic and gallbladder cancer, although trials are underway. References: Le D, et al. N Engl J Med. 2015, p. 2509-2520. Ed. 372.

Question 108

            How many mitotic figures per 10 HPF (high power field) define grade III meningiomas?

Answer 108

            ?20 = Rationale: Meningiomas are graded by mitotic activity, among other features. Grade III meningiomas have 20 or more mitotic figures per 10 HPF.

Question 109

            A two-armed clinical trial randomized 40 subjects into group A or group B, and the outcome of interest is the change in serum cholesterol. The observed mean difference of the changes between two groups is 2.5mg/dl. What additional information is needed to determine the difference between the two arms?

Answer 109

            Standard Deviation = Rationale: In order to answer this question, we need to know the standard deviation of the difference of change in serum cholesterol between two groups. If the standard deviation is given, we can derive 95% confidence interval of the difference between two treatments. If the 95% confidence interval does not contain 0, then we reject the null hypothesis and make the conclusion-there is statistical difference between the treatments.

Question 110

            What is a consequence of contouring the target volume on a misregistered MRI (incorrectly aligned to simulation CT) during treatment planning?

Answer 110

            Geographic miss of the target = Rationale: If a target volume is inaccurately contoured on the CT (not MR), it could result in a geographic miss.

Question 111

            Regarding the NSABP analysis of 21-Gene Recurrence Score Assay, what is the relationship between the recurrence score and locoregional recurrence at 10 years?

Answer 111

            For patients treated with chemotherapy and tamoxifen, the LRR was < 10% regardless of score . = Rationale: Age < 50 was a significant risk factor for locoregional recurrence with a p-value of 0.0002 and HR of 0.4. Placebo treated patients with low Oncotype scores had a LRR risk of 10.8%. The axilla was the most common site of regional failure. LRR risk ranged from 1.6 – 7.8% between the low and high-risk groups.

Question 112

            What type of clinical trial evaluates the efficacy and toxicity of a drug after post-market approval?

Answer 112

            Phase IV = Rationale: A Phase IV clinical trial is a post-marketing surveillance study to evaluate the real-world effectiveness of a drug in an observational, non-interventional setting complementing the efficacy determined by pre-marketing randomized trial.

Question 113

            For a TG-51 calibration of a 6 MeV electron beam using a parallel-plate chamber, where is the effective point of measurement located?

Answer 113

            Top surface of the collection volume = Rationale: The effective point of measurement for a parallel-plate chamber is at the top surface of the collection volume.

Question 114

            After a radical inguinal orchiectomy for a stage I seminoma, pathology demonstrates a 3.4 cm tumor with rete teste involvement, no LVSI and a negative spermatic cord margin. What is the risk of relapse with surveillance?

Answer 114

            16% = Rationale: After radical surgery, multiple prognostic factors have been identified that are associated with risk of relapse if no further adjuvant therapy is given. These include size> 4cm, LVSI, and rete testis involvement. Relapse risk is as follows: No risk factors: 12%; 1 risk factor: 16%; 2 risk factors: 30%. References: Warde et al., Journal of clinical oncology, 15 Nov 2002, 20(22):4448-52.

Question 115

            Which mechanism is involved with silencing oncogene expression?

Answer 115

            DNA methylation = Rationale: DNA methylation is associated with the silencing of gene expression and is typically associated with tumor suppressor gene silencing. Gene amplification, point mutations and chromosomal translocations are all associated with excess normal protein expression or abnormal (hyperactive) protein expression which are key features on oncogenes.

Question 116

            From Japanese bomb survivors' data, what radiation effect was seen for embryos irradiated beyond 20 weeks gestation, compared with 7 week gestation?

Answer 116

            Lower risk of retardation = Rationale: The effects of radiation to the embryo and fetus depend upon the stage of gestation, the dose, and the dose rate. Congenital malformations are seen with radiation in the early (2-6 weeks) phases of development. Severe mental retardation is nearly 4 times more common if the radiation is received between 8 and 15 weeks than if it is received later. Children exposed in utero are shorter, lighter, and have a smaller head diameter than those not exposed to radiation.

Question 117

            In patients treated with prior mastectomy and axillary nodal staging and no post mastectomy radiation, where is the most common site of locoregional recurrence?

Answer 117

            Chest wall = Rationale: The most frequent site of locoregionaI recurrence after mastectomy without post mastectomy radiation is the chest wall, followed by the axillary and supraclavicular nodal regions. Following LRR, rates of subsequent metastases are high, indicating many women with LRR with die of breast cancer. On multivariate analysis nodal failures (as compared to chest wall recurrences) and disease-free interval less than 2 years were unfavorable. Those women treated with both surgery and RT had improved loco-regional control from women treated with a single modality.

Question 118

            Which clinical or pathologic feature would meet eligibility criteria for the RTOG 9804 trial of radiation versus observation for good-risk DCIS?

Answer 118

            2 cm intermediate grade = Rationale: Eligiblity for RTOG 9804 included: women with DCIS detected by mammogram or incidentally found in tissue of an otherwise benign biopsy; unicentric, low or intermediate nuclear grade DCIS less than 2.5 cm; with minimal margin width of 3 mm. All patients had a negative post-excision mammogram. Patients were randomized to breast RT versus no RT. With a median follow up of 7 years, 7-year risk of in-breast recurrence was 6.7% with no RT and 0.9% with RT.

Question 119

            Which laboratory assay measures in vivo local control of a cancer by radiation (or chemoRT)?

Answer 119

            TCD50 assay = Rationale: Tail vein injection assays are designed to assess the ability of a cell to extravasate from the bloodstream and develop metastatic deposits. Wound healing assays are in vitro assays that investigate the ability of a cell to migrate across a “wound.” Spheroid growth assays assess the growth of tumor cell in three-dimensional in vitro culture. TCD50 assays are used to determine the dose of radiation required to achieve local control in 50% of tumors. References: Hall and Giaccia. Radiobiology for the Radiologist, Lippincott, Williams and Wilkins, Chapter 20, Sixth Edition, 2006, 358-359.

Question 120

            What was the peak latent period for leukemia induction seen in the Japanese bomb survivors?

Answer 120

            5-8 years = Rationale: The latent period is the time between radiation exposure and the appearance of the malignancy. For the Japanese atomic bomb survivors the incidence of leukemia reached a peak in 5 to 7 years with most cases reported before 15 years since the attack.

Question 121

            When using brachytherapy as a boost treatment for vaginal cancer, what is the maximum tumor thickness for which an intracavitary cylinder implant can be used?

Answer 121

            5 mm = Rationale: Residual vaginal tumors less than 5 mm thickness can be treated with intracavitary vaginal brachytherapy. Thicker tumors should be considered for interstitial if using brachytherapy as a boost. References: ACR Appropriateness Criteria Management of Vaginal Cancer 2013.

Question 122

            A patient had a partial glossectomy and neck dissection for T2N1 squamous cell carcinoma of the oral tongue with extranodal extension. Which is the most appropriate adjuvant treatment?

Answer 122

            Radiation therapy and concurrent chemotherapy = Rationale: The RTOG 9501 and EORTC 22931 trials compared adjuvant radiation therapy versus adjuvant radiation therapy and concurrent bolus cisplatin in resected head and neck squamous cell carcinoma. The combined analysis showed an overall survival benefit for patients with positive margins and extranodal extension. References: Cooper, New England Journal of Medicine, 2004, 350(19):1937-1944.