21 Radiation & Systemic Therapy for Head & Neck Cancer Flashcards Preview

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Flashcards in 21 Radiation & Systemic Therapy for Head & Neck Cancer Deck (27):
1

What is radiation therapy (RT) and what are the common techniques used in treating cancers of the head and neck (HN)?

What is radiation therapy (RT) and what are the common techniques used in treating cancers of the head and neck (HN)?

Radiotherapy, also called radiation therapy, is the localized treatment of cancer and other diseases with ionizing radiation. Ionizing radiation induces mitotic cell death via damage to DNA through a variety of atomic interactions including free radical generation and direct DNA strand breaks. The primary goal of all RT is to maximize cell kill of the target (e.g., cancer cells) while minimizing damage to healthy normal tissues. Radiation is most commonly delivered by an external source (i.e., external beam radiotherapy [EBRT]) using electrons, photons, protons, and other heavy particles, but may also be administered by temporarily or permanently placing radioactive sources into a patient’s body (i.e., brachytherapy). Patients are not radioactive when treated with EBRT. The most frequently used modern EBRT techniques for treatment of head and neck cancers are three-dimensional conformal radiotherapy (3DCRT) and the more complex method of intensity modulated radiotherapy (IMRT). Varying dose rates/energies, multiple beam angles/arcs, and dynamic multileaf collimator shapes combine to optimize delivery of the radiation. Image-guided radiotherapy (IGRT) uses imaging capabilities on the treatment machine (e.g., X-rays and cone-beam CT scans) to verify patient setup. Stereotactic body RT (SBRT) is an additional technique often used in the palliative or re-irradiation setting that delivers high doses of radiation in five or fewer treatments (Figure 21-1).

2

Who should evaluate a patient prior to initiating RT with or without systemic therapy?

Who should evaluate a patient prior to initiating RT with or without systemic therapy?

Patients undergoing radiation treatment for head and neck cancers require timely coordination and support from a multitude of care providers. Multidisciplinary evaluation and tumor board discussion of a patient’s case can be critical for providing optimal care. The following specialists will often be involved:

  • Radiation oncologist: A formal H&P evaluation and review of all available imaging is necessary to determine the appropriate radiation targets, dosing, and schedule.
  • Medical oncologist: A formal medical oncology evaluation is recommended for any patient that may be a candidate for systemic therapies.
  • Dentist or oral surgeon: Any patient who may receive radiation in the region of the mandible, maxilla, or teeth should receive a formal evaluation and any necessary dental work (e.g., extraction of unhealthy teeth, fillings, fluoride trays) prior to initiating RT. Most institutions require a minimum of 2 to 4 weeks healing prior to starting radiation. A delay in the dental evaluation is one of the most common yet significant causes of delay in initiating RT. For patients with clearly unhealthy teeth who undergo initial surgical resection, teeth extractions are often performed by the otolaryngologist in anticipation of adjuvant RT.
  • Nutritionist: Regular assessments of nutritional status for HN cancer patients before, during, and after RT and systemic therapy are critical. Nutritionists can also provide teaching and support for patients with feeding tubes.
  • Speech and swallow therapy: A baseline evaluation is recommended for patients with current or anticipated speech or swallowing problems.
  • Pathology, radiology, and otolaryngologist: Involvement is recommended to help with RT planning.
  • Additional consultants: May include interventional radiology, audiology, ophthalmology, neurosurgery, plastic surgery, physical medicine and rehabilitation, social work, addiction services, and palliative care.

3 Beyond initial multidisciplinary consultations, what are the specific steps necessary for a patient with head and neck cancer to receive radiation?

CT simulation: Planning, or simulation, CT scans are performed in the radiation oncology department at which time immobilization devices customized to the patient are made including a thermoplastic molded mask, a mouth piece, and a head rest. MRI, PET/CT, and additional scans may be performed to assist with both staging and treatment planning. Whenever possible, patients should receive these additional scans in the radiation treatment position using their mask, mouth piece, and head rest to assist with immobilization. Having similar positions between all imaging modalities optimizes the accuracy of image fusions used for target delineation planning software (Figure 21-1).

Drawing volumes: The radiation oncologist will then use planning software to outline gross tumor, areas of potential microscopic disease, and normal tissues. This process is known as “drawing volumes,” often takes several hours, and may involve more than twenty distinct volumes or structures.

Planning: A dosimetrist, physicist, and the radiation oncologist then work together to create the optimal plan for delivering the radiation to the target while restricting the dose to normal tissues. These plans are often reviewed by multiple people and run through quality assurance checks on the treatment machine.

Treatment: Radiation treatment for HN cancer patients often involves once daily radiation for 6 to 7 weeks with weekly check-up appointments with the radiation oncologist to evaluate and treat toxicities.

4 How do radiation and surgery compare to each other?

Both RT and surgery are local therapies. Definitive RT strives for organ preservation to maintain critical functions such as swallowing, normal speech, and airway protection, and attempting to maximize quality of life in patients that might otherwise undergo significantly morbid surgeries. Additionally, RT is typically delivered daily Monday through Friday over 6 to 8 weeks on an outpatient basis without need of anesthesia, making it an ideal modality for poor surgical candidates. This protracted time commitment can be problematic for noncompliant or elderly patients and those living great distances from a radiation oncology facility. Surgery is advantageous in providing a one-time procedure and optimal pathologic assessment of primary tumors and nodal disease. While acute side effects of surgery occur primarily in the immediate postoperative time frame, acute RT toxicities typically build up gradually throughout the course of treatment. Extent of disease and involvement of critical structures limits both surgeons in their ability to achieve complete resection of disease and radiation oncologists in their ability to treat these disease sites to full definitive doses. Both specialties must balance aggressive treatment with acute and long-term local toxicities.

5 What are the general doses used in RT for HN cancers?

A Gray (Gy) represents one joule per kilogram and is the standard unit of absorbed dose used in clinical radiation oncology. A variety of doses and fractionation schedules are used in treating HN cancers. In the typical daily radiation setting, daily doses of 180 to 225 cGy (1.8 to 2.25 Gy) are used. General, non–site specific total doses vary based on the setting (definitive RT to gross disease ≈66 to 70 Gy; high-risk elective neck coverage ≈60 Gy; low-risk elective neck ≈54 Gy; and postoperative RT ≈66 Gy).

3

Beyond initial multidisciplinary consultations, what are the specific steps necessary for a patient with head and neck cancer to receive radiation?

Beyond initial multidisciplinary consultations, what are the specific steps necessary for a patient with head and neck cancer to receive radiation?

  • CT simulation: Planning, or simulation, CT scans are performed in the radiation oncology department at which time immobilization devices customized to the patient are made including a thermoplastic molded mask, a mouth piece, and a head rest. MRI, PET/CT, and additional scans may be performed to assist with both staging and treatment planning. Whenever possible, patients should receive these additional scans in the radiation treatment position using their mask, mouth piece, and head rest to assist with immobilization. Having similar positions between all imaging modalities optimizes the accuracy of image fusions used for target delineation planning software (Figure 21-1).
  • Drawing volumes: The radiation oncologist will then use planning software to outline gross tumor, areas of potential microscopic disease, and normal tissues. This process is known as “drawing volumes,” often takes several hours, and may involve more than twenty distinct volumes or structures.
  • Planning: A dosimetrist, physicist, and the radiation oncologist then work together to create the optimal plan for delivering the radiation to the target while restricting the dose to normal tissues. These plans are often reviewed by multiple people and run through quality assurance checks on the treatment machine.
  • Treatment: Radiation treatment for HN cancer patients often involves once daily radiation for 6 to 7 weeks with weekly check-up appointments with the radiation oncologist to evaluate and treat toxicities.

4

How do radiation and surgery compare to each other?

How do radiation and surgery compare to each other?

Both RT and surgery are local therapies. Definitive RT strives for organ preservation to maintain critical functions such as swallowing, normal speech, and airway protection, and attempting to maximize quality of life in patients that might otherwise undergo significantly morbid surgeries. Additionally, RT is typically delivered daily Monday through Friday over 6 to 8 weeks on an outpatient basis without need of anesthesia, making it an ideal modality for poor surgical candidates. This protracted time commitment can be problematic for noncompliant or elderly patients and those living great distances from a radiation oncology facility. Surgery is advantageous in providing a one-time procedure and optimal pathologic assessment of primary tumors and nodal disease. While acute side effects of surgery occur primarily in the immediate postoperative time frame, acute RT toxicities typically build up gradually throughout the course of treatment. Extent of disease and involvement of critical structures limits both surgeons in their ability to achieve complete resection of disease and radiation oncologists in their ability to treat these disease sites to full definitive doses. Both specialties must balance aggressive treatment with acute and long-term local toxicities.

5

What are the general doses used in RT for HN cancers?

What are the general doses used in RT for HN cancers?

A Gray (Gy) represents one joule per kilogram and is the standard unit of absorbed dose used in clinical radiation oncology. A variety of doses and fractionation schedules are used in treating HN cancers. In the typical daily radiation setting, daily doses of 180 to 225 cGy (1.8 to 2.25 Gy) are used. General, non–site specific total doses vary based on the setting (definitive RT to gross disease ≈66 to 70 Gy; high-risk elective neck coverage ≈60 Gy; low-risk elective neck ≈54 Gy; and postoperative RT ≈66 Gy).

6

Who cannot be treated with RT?

Who cannot be treated with RT?

Patients who should not receive radiation are those with collagen-vascular diseases, other hypersensitivity conditions (e.g., ataxia-telangiectasia), pregnant women particularly in the first two trimesters, and those who would exceed maximum safe cumulative doses of RT to critical structures. Some patients can be retreated, usually with a lower dose, after time has elapsed since the previous treatment. Additionally, disorders of DNA repair and conditions (e.g., Li-Fraumeni syndrome and xeroderma pigmentosum) put patients at high risk for radiation induced secondary cancers.

7

What is systemic therapy and how does it work both with and without radiation?

What is systemic therapy and how does it work both with and without radiation?

Chemotherapy and biologics are the two main groups of systemic therapies. These treatments deliver cytotoxic drugs or molecularly targeted therapeutic agents that travel through the bloodstream with the goal of treating cancer cells throughout the body. Cytotoxic drugs interfere with DNA replication, microtubule formation, and other cellular processes to impair mitosis and/or induce apoptosis. While these agents tend to primarily damage cells with high mitotic rates (e.g., cancer, mucosal tissues, and bone marrow), they are fairly indiscriminate. Biologics, in turn, typically employ antibodies to specifically target proteins ubiquitous among a clonal cancer cell population such as a surface antigen and/or components critical to a cancer signaling pathway. Often times concurrent chemoradiation (CRT) or radiation with targeted therapies provides a synergistic effect allowing improved tumor control. The systemic therapy can put cancer cells into a radiosensitive state by manipulation of the proliferative pathways.

8

What are the most common systemic agents used in treatment of nonmetastatic HN cancers and their associated toxicities?

What are the most common systemic agents used in treatment of nonmetastatic HN cancers and their associated toxicities?

Cisplatin is the most commonly used systemic therapy in both the induction and concurrent setting. For concurrent chemoradiation, high-dose cisplatin is given weekly or every 3 weeks. Systemic agents most often used for treatment of nonmetastatic head and neck cancers, along with their main adverse effects are reported in Table 21-1.

9

How is systemic therapy used in the treatment of head and neck cancers?

How is systemic therapy used in the treatment of head and neck cancers?

Systemic therapy may be administered in the following settings with different goals:

  • Neoadjuvant or induction: Given prior to definitive treatment (i.e., surgery or radiation) to decrease the size/extent of cancer to allow for less extensive local treatment, and in some cases allow for organ preservation.
  • Adjuvant: Given after definitive treatment with hopes of decreasing recurrence either locally or distally (not currently standard of care in HN cancers)
  • Concomitant or concurrent with radiation: Used to augment the efficacy of radiation via radiosensitization. In this setting, the systemic therapy is not thought to significantly improve control of undetectable metastatic disease.
  • Metastatic: Primarily used to prolong disease control and palliate symptoms.

10

Who should receive induction therapy?

Who should receive induction therapy?

Multiple randomized trials have demonstrated no significant benefits of induction chemotherapy prior to definitive treatment of SCC of the head and neck. Some evidence exists for a reduction of distant metastases and improved organ preservation in hypopharynx and nasopharynx cancers, but the role of induction chemotherapy remains controversial. Currently, induction chemotherapy should be considered only in clinical trials or in select conditions (e.g., upper airway obstruction or dental abscesses) due to delays in initiation of definitive concurrent chemoradiation. Multidisciplinary tumor board review and treatment at experienced tertiary care centers are highly recommended when considering induction therapy.

11

What is the role of cetuximab in treating HN cancers?

What is the role of cetuximab in treating HN cancers?

Cetuximab is a monoclonal antibody that targets the extracellular domain of endothelial growth factor receptor (EGFR). EGFR is frequently mutated and/or overexpressed in HN cancers. While cisplatin remains the gold standard systemic therapy in concurrent chemoradiation setting, cetuximab is an FDA approved alternative with a different side effect profile making it a suitable alternative in select situations (e.g., following a cisplatin based induction regimen).

12

Which tumors can be definitively treated with radiation as the sole treatment modality and when should concurrent systemic therapy be added?

Which tumors can be definitively treated with radiation as the sole treatment modality and when should concurrent systemic therapy be added?

Surgery is often preferred in the setting where complete resection with sufficient margins can be expected without causing significant morbidity; however, nearly all early stage head and neck cancers that are T1 to T2 and N0-1 are candidates for definitive RT alone. These include primary tumors of the tongue, tonsil, larynx, and hypopharynx. Exceptions include cancers of the nasopharynx, in which external beam RT is the standard treatment regardless of T or N stage. Tumors of the salivary glands and floor of the mouth are generally managed primarily with surgery, even if diagnosed at an early stage.

Concurrent systemic therapy should be added to radiation for more advanced (e.g., T3–T4, N2–N3) head and neck tumors. Multiple randomized trials and meta-analyses have shown an absolute survival benefit in this setting.

13

What are the standard indications for adjuvant RT and/or systemic therapy after surgical resection of a SCC head and neck tumor?

What are the standard indications for adjuvant RT and/or systemic therapy after surgical resection of a SCC head and neck tumor?

Positive margins, T3–4 tumors, multiple or bulky positive lymph nodes, nodal extracapsular extension (ECE), perineural invasion (PNI), lymphovascular invasion (LVI), or nodal disease in levels IV or V. Additionally, oral cavity cancers with depth of invasion greater than 2 mm or close margins should receive adjuvant radiation. In most cases, patients with recurrent disease treated with salvage surgery should be offered adjuvant radiation therapy when feasible.

14

What are the standard indications for concurrent chemotherapy with RT after surgical resection of an SCC head and neck tumor?

What are the standard indications for concurrent chemotherapy with RT after surgical resection of an SCC head and neck tumor?

The addition of concurrent chemotherapy to adjuvant radiation is typically recommended for patients with positive margins or ECE. Two major randomized trials (i.e., RTOG 95-01 and EORTC 22931) have examined adjuvant radiation with or without concomitant cisplatin with results showing local control, disease-free survival, and possibly overall survival benefits when using combined modality treatment.

15

What are the indications for adjuvant RT after surgical resection for salivary gland tumors?

What are the indications for adjuvant RT after surgical resection for salivary gland tumors?

For salivary gland tumors, adjuvant RT should be offered to patients with close or positive margins, pT3–4 tumors, intermediate/high grade, adenoid cystic carcinoma histology, bone invasion, PNI, LVI, and pathologic node positive disease. The addition of concurrent chemotherapy may be considered on a case by case basis and is the subject of multiple ongoing trials. For salivary gland tumors, postoperative radiation also improves overall survival in addition to local regional control in patients with high-grade histology or locally advanced tumors.

16

What is the recommended time between surgery and initiation of adjuvant RT for most HN cancers?

What is the recommended time between surgery and initiation of adjuvant RT for most HN cancers?

Generally 4 to 6 weeks is recommended because there is a direct correlation between the time to initiation of postoperative RT and tumor control outcomes, but patients must be well healed before starting radiation. Several studies have validated the importance of a timely “package time” being ≈13 weeks from date of surgery to completion of adjuvant radiation. Delays or breaks in treatment are associated with poor outcomes for two primary reasons: (1) HN cancers exhibit accelerated repopulation and (2) an inherent bias exists in that patients with advanced disease tolerate treatment poorly and require these delays and breaks.

17

When delivering RT for an HN cancer of unknown primary, which areas should be treated?

When delivering RT for an HN cancer of unknown primary, which areas should be treated?

Possible primary mucosal sites that commonly metastasize, including the nasopharynx and oropharynx, and bilateral neck (unilateral coverage is controversial). The larynx, hypopharynx, and oral cavity may be treated if the patient is suspected to be at high risk in those areas.

18

Does HPV status, p16 status, or any other molecular markers affect the recommended doses for RT?

Does HPV status, p16 status, or any other molecular markers affect the recommended doses for RT?

No. Currently no molecular markers support escalation or de-escalation of the standard recommendations for radiation dosing. While HPV(+) and p16(+) oropharynx patients have better outcomes, and retrospective data shows favorable outcomes with dose de-escalation, no level 1 evidence exists for de-escalation. Treatment deintensification is an active area of research.

19

Which head and neck skin cancer patients should be considered for definitive radiation?

Which head and neck skin cancer patients should be considered for definitive radiation?

Patients with large lesions that would require significant morbid surgeries, those with lesions of the central face or other locations for which surgery would result in significant cosmetic defects (e.g., nasal ala), and nonsurgical candidates.

20

What are the indications for adjuvant therapy after surgical resection for head and neck skin cancers?

What are the indications for adjuvant therapy after surgical resection for head and neck skin cancers?

Perineural invasion, positive surgical margins, parotid invasion, or an ear primary with high-risk features (i.e., depth of invasion >2 mm, Clark’s level ≥IV, poor differentiation).

21

What features of a primary skin cancer warrant elective nodal irradiation?

What features of a primary skin cancer warrant elective nodal irradiation?

Multiple positive lymph nodes (>3), extracapsular extension, large tumors (>4 cm), deep invasion of underlying structures (e.g., cartilage), or cancer of the ear, particularly preauricular.

22

What are the common acute adverse effects of RT to the head and neck region and how are they managed?

What are the common acute adverse effects of RT to the head and neck region and how are they managed?

The acute side effects of RT usually appear in weeks 2 to 3, gradually progress through the week after the last radiation treatment, and resolve within 4 to 6 weeks after completion. Toxicities are often worse with concurrent systemic therapy. Optimal supportive management is necessary to avoid treatment breaks which have been proven to decrease treatment efficacy. Supportive treatments for the most common symptoms include the following:

  • Fatigue: An active exercise regimen and general healthy lifestyle practices, psychostimulants, and antidepressants
  • Skin reactions: Nonperfumed moisturizers and humectants
  • Mucositis, dysphagia, odynophagia: Dietary modifications, green tea, Manuka honey, liquid lidocaine, benadryl, antacids, NSAIDs, narcotics, sucralfate, steroids, and optimal hydration/nutrition support which sometimes includes feeding tube placement
  • Xerostomia: Mouth rinses (including combinations of water, baking soda, salt, hydrogen peroxide), biotin, pilocarpine, prophylactic amifostene, and optimal oral hygiene

Depending on the site receiving radiation, hoarseness, otitis media, dry eyes, conjunctivitis/keratitis, sinonasal congestion, and epistaxis may also occur.

23

Why is hydration/nutrition important for patients receiving radiation and/or systemic therapies for head and neck tumors?

Why is hydration/nutrition important for patients receiving radiation and/or systemic therapies for head and neck tumors?

Most of these patients are nutritionally depleted due to the morbidity of the tumor itself. Mucositis, nausea, vomiting, and anorexia from multimodality treatments add to the nutritional depletion, compounding the weight loss. Poor nutrition or hydration may lead to hospitalization and treatment breaks. In addition, patients that lose significant amounts of weight may not align correctly in their positioning masks for radiation which can require replanning with treatment breaks. Treatment breaks, while sometimes necessary, decrease cure rates and should be avoided when at all possible. Enteral gastrostomy feedings are often used when patients receive bilateral neck radiation to support nutrition and hydration.

24

What are the potential long-term complications of RT?

What are the potential long-term complications of RT?

Serious radiation complications are unusual (with an incidence of less than 10%) but are difficult to manage when they occur. The likelihood of a given patient developing long-term complications depends on the total dose of radiation delivered, the dose per fraction, the time frame over which it was given, and the anatomic sites included within the radiation portal. In general, the risk increases with increasing doses delivered over shorter time periods to greater volumes of tissue. Complications include xerostomia, skin changes, hypothyroidism, osteoradionecrosis, bone exposure, laryngeal edema with voice changes, esophageal stenosis, vision/hearing deficits, fibrosis including trismus, and induction of secondary cancers. Xerostomia is one of the most common and bothersome long-term side effects of head and neck irradiation. When possible, attempts should be made to minimize doses to parotid and submandibular glands without sacrificing tumor coverage. Dry mouth also causes an increased risk of developing dental carries with subsequent increased risk for osteoradionecrosis.

25

What is the benefit of intensity-modulated radiotherapy (IMRT) in treating HN cancers?

What is the benefit of intensity-modulated radiotherapy (IMRT) in treating HN cancers?

IMRT has become the standard RT technique for head and neck cancers in the past 15 years and multiple trials have shown an ability to achieve similar rates of local control while lowering the incidence of acute and long-term toxicities by decreasing radiation dose to critical organs (e.g., salivary glands for xerostomia, constrictor muscles for dysphagia).

26

When should a neck dissection be performed after definitive RT?

When should a neck dissection be performed after definitive RT?

Patients with clinical or radiographic residual gross nodal disease or initially bulky nodal disease should be considered for post-RT neck dissection. A balance is necessary as tumors can take weeks to months to respond to radiation therapy yet fibrosis can develop in a similar time frame, which can make surgery difficult. The response to radiation treatment is generally assessed by PET/CT at 12 weeks post-treatment.

27

When should re-irradiation be considered?

When should re-irradiation be considered?

Recurrent disease, when the patient is not eligible for salvage surgery or with post salvage surgery high-risk features, may be considered for re-irradiation. In the re-irradiation setting, the risks for both acute and long term toxicities are increased. Stereotactic body radiotherapy (SBRT) is one technique under investigation for use in the re-irradiation setting as a means of delivering highly conformal high-dose radiation to areas of relapse while sparing normal tissues.

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