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Question 1

What is the main treatment investigated in the INTERLACE trial for locally advanced cervical cancer?

Answer 1

Chemoradiotherapy with or without induction chemotherapy

The trial aimed to determine if induction chemotherapy improves progression-free and overall survival.

Question 2

What were the primary endpoints of the INTERLACE trial?

Answer 2

Progression-free survival and overall survival

These endpoints were assessed within the intention-to-treat population.

Question 3

In which countries was the INTERLACE trial conducted?

Answer 3

Brazil, India, Italy, Mexico, and the UK

The trial involved 32 medical centres across these countries.

Question 4

What was the randomization ratio for patients in the INTERLACE trial?

Answer 4

1:1

Patients were randomly assigned to either standard chemoradiotherapy alone or induction chemotherapy followed by standard chemoradiotherapy.

Question 5

What was the age requirement for participants in the INTERLACE trial?

Answer 5

≥18 years

Only adults with locally advanced cervical cancer were eligible for the trial.

Question 6

What types of histology were eligible for the INTERLACE trial?

Answer 6

• Squamous
• Adenocarcinoma
• Adenosquamous

Patients had to have histologically confirmed locally advanced cervical cancer.

Question 7

What was the median follow-up period for patients in the INTERLACE trial?

Answer 7

67 months

This duration was used to assess progression-free and overall survival rates.

Question 8

What was the 5-year progression-free survival rate for the induction chemotherapy group?

Answer 8

72%

This was compared to a 64% rate in the chemoradiotherapy alone group.

Question 9

What was the 5-year overall survival rate for the induction chemotherapy group?

Answer 9

80%

This contrasted with a 72% survival rate in the chemoradiotherapy alone group.

Question 10

What percentage of patients in the induction chemotherapy group received at least five cycles?

Answer 10

92%

This indicates a high adherence to the treatment regimen.

Question 11

What were the grade 3 or greater adverse event rates for the two groups?

Answer 11

• Induction chemotherapy group: 59%
• Chemoradiotherapy alone group: 48%

Adverse events were more common in the induction chemotherapy group.

Question 12

What is the purpose of induction chemotherapy in the context of this trial?

Answer 12

To reduce tumour volume and micrometastatic disease

This approach aims to improve outcomes before definitive treatment.

Question 13

What are the key exclusion criteria for the INTERLACE trial?

Answer 13

• FIGO 2008 stage IIIA disease
• Presence of para-aortic nodes

These exclusions were based on treatment uncertainties for these patients.

Question 14

What statistical method was used to randomize patients in the INTERLACE trial?

Answer 14

Minimisation using a central electronic system

This method helped ensure balanced allocation across various factors.

Question 15

What was the maximum overall radiation treatment time allowed in the trial?

Answer 15

50 days

With possible extensions up to 56 days with Trial Management Group’s approval.

Question 16

What was the initial target accrual number for the INTERLACE trial?

Answer 16

700 patients

This was later reduced to 500 due to slower than expected recruitment.

Question 17

What is the significance of the hazard ratio (HR) in the study results?

Answer 17

It indicates the risk of progression or death

An HR of 0.65 for progression-free survival suggests a lower risk in the induction chemotherapy group.

Question 18

True or False: The INTERLACE trial showed that induction chemotherapy improves survival outcomes for patients with locally advanced cervical cancer.

Answer 18

True

The trial concluded that induction chemotherapy significantly improves survival.

Question 19

What are the primary endpoints measured in the study?

Answer 19

Adverse events, pattern of first relapse, time to next anticancer therapy, health-related QoL using EORTC QLQ-C30 and QLQ-CX24

EORTC stands for European Organisation for Research and Treatment of Cancer.

Question 20

What was the initial target patient accrual for the study?

Answer 20

700 patients

Question 21

What was the final target patient accrual after adjustments?

Answer 21

500 patients

Question 22

What statistical method was used to analyze overall survival and progression-free survival?

Answer 22

Kaplan–Meier plots and Cox proportional hazards regression

Question 23

What was the significance level and power assumed for the study?

Answer 23

Two-sided 5% significance level with 70–84% power

Question 24

What was the required number of events to detect a hazard ratio for overall survival?

Answer 24

At least 192 deaths

Question 25

What was the hazard ratio for progression-free survival in the study?

Answer 25

0·G5

Question 26

What was the median age of patients recruited in the study?

Answer 26

4G years

Question 27

What percentage of patients had FIGO 2008 stage IIB disease?

Answer 27

71%

Question 28

What percentage of patients completed five cycles of cisplatin in the induction chemotherapy with chemoradiotherapy group?

Answer 28

68%

Question 29

What were the main reasons for not completing six cycles of chemotherapy?

Answer 29

Neutropenia, hypersensitivity reactions, patient or clinician decisions, renal toxicity, withdrawal

Question 30

What was the median interval from induction chemotherapy completion to chemoradiotherapy start?

Answer 30

7 days

Question 31

What percentage of patients in the induction chemotherapy group received definitive EBRT?

Answer 31

98%

Question 32

What was the median total 2 Gy equivalent dose for all patients?

Answer 32

79·4 Gy

Question 33

What percentage of patients received brachytherapy in the induction chemotherapy group?

Answer 33

98%

Question 34

What was the absolute risk difference at 3 years for progression-free survival?

Answer 34

8·7 percentage points

Question 35

Was there a correlation between the time to start treatment and subsequent relapse in the chemoradiotherapy alone group?

Answer 35

No

Question 36

What was the HR for overall survival in the study?

Answer 36

0·G0

Question 37

What percentage of patients had local or pelvic relapse in the induction chemotherapy group?

Answer 37

11%

Question 38

True or False: More patients had distant only relapses in the induction chemotherapy with chemoradiotherapy group compared to the chemoradiotherapy alone group.

Answer 38

False

Question 39

What percentage of patients experienced grade 3–4 adverse events in the induction chemotherapy group?

Answer 39

59%

Question 40

What was the most common grade 3–4 adverse event in the induction chemotherapy group?

Answer 40

Neutropenia

Question 41

Fill in the blank: The median follow-up for patients at the time of analysis was ______ months.

Answer 41

G7

Question 42

What was the percentage of patients in the chemoradiotherapy alone group who completed at least four cycles of cisplatin?

Answer 42

90%

Question 43

What was the range of the median total HRCTV D90 EQD2 for patients treated with IGABT?

Answer 43

5G·3–120·9 Gy

Question 44

What percentage of patients in the induction chemotherapy with chemoradiotherapy group experienced a grade 3–4 adverse event during the induction phase?

Answer 44

22% ## Footnote Out of 250 patients, 54 had such events.

Question 45

What was the most common grade 3–4 adverse event reported?

Answer 45

Neutropenia (7%) ## Footnote Other adverse events had a frequency of less than 3%.

Question 46

How many patients reported hair loss as grade 1 and grade 2?

Answer 46

* Grade 1: 39 patients (1G%) * Grade 2: 10 patients (42%) ## Footnote Scalp cooling was permitted, though its usage is not recorded.

Question 47

What was the HR for time to next anticancer therapy comparing induction chemotherapy with chemoradiotherapy versus chemoradiotherapy alone?

Answer 47

0.54 (95% CI 0.38–0.77), p=0.0010 ## Footnote This indicates a significant improvement in the induction chemotherapy group.

Question 48

What was the mean change in QoL scores during induction chemotherapy treatment?

Answer 48

Generally less than 5 units ## Footnote This change is not clinically relevant on a scale of 0–100.

Question 49

What improvement in progression-free survival rate was observed with the induction chemotherapy regimen?

Answer 49

11 percentage points ## Footnote This improvement was statistically significant.

Question 50

What type of toxicity was more common with induction chemotherapy?

Answer 50

Haematological toxicity (mainly neutropenia) ## Footnote Monitoring of blood counts and GCSF intervention is recommended.

Question 51

What was the percentage of patients who received EBRT in the induction chemotherapy group?

Answer 51

98% ## Footnote The adherence to chemoradiotherapy was high and similar between both trial groups.

Question 52

What percentage of patients in the INTERLACE trial had FIGO 2018 stage IIIC1 disease?

Answer 52

40% in induction chemotherapy group, 43% in chemoradiotherapy group ## Footnote This highlights the high-risk nature of the patient population.

Question 53

What was the median overall radiation treatment time in both groups of the trial?

Answer 53

45 days ## Footnote 97% of patients completed radiotherapy within 56 days.

Question 54

True or False: There was a significant difference in distant relapses between the two groups.

Answer 54

False ## Footnote Distant only relapses were more frequent in the chemoradiotherapy alone group.

Question 55

What is the FDA's restriction regarding pembrolizumab in locally advanced cervical cancer?

Answer 55

Restricted to patients with stage III disease or IVA disease only ## Footnote This follows findings that pembrolizumab improved progression-free survival.

Question 56

Fill in the blank: The short-course induction chemotherapy regimen should now be considered a _______.

Answer 56

standard treatment for locally advanced cervical cancer ## Footnote It improves survival when followed by chemoradiotherapy within 7 days.

Question 57

What was the duration of the INTERLACE trial's recruitment period?

Answer 57

10 years ## Footnote This duration was influenced by strict quality assurance requirements and patient concerns.

Question 58

What percentage of patients had isolated para-aortic nodal recurrences in the trial?

Answer 58

Only one patient in the induction chemotherapy group and three in the chemoradiotherapy alone group ## Footnote This suggests effective control of distant micrometastatic disease.

Question 59

What is the main conclusion regarding the short-course induction chemotherapy regimen for locally advanced cervical cancer?

Answer 59

It improves survival and should be considered a standard of care ## Footnote This regimen should be included in future trials exploring new treatment agents.

Question 60

What percentage of patients diagnosed with cervical cancer have locally advanced disease?

Answer 60

37% ## Footnote This statistic indicates a significant number of patients who could benefit from neoadjuvant therapy.

Question 61

Which two drugs are mentioned as affordable and effective for neoadjuvant therapy in cervical cancer?

Answer 61

Cisplatin and paclitaxel ## Footnote These drugs are readily available and used before chemoradiotherapy.

Question 62

What is the role of MM in the trial mentioned?

Answer 62

Conceptualised the trial and wrote the first draft of the manuscript ## Footnote MM collaborated with other authors for input and final drafting.

Question 63

True or False: Recommendations on neoadjuvant therapy are consistent across all countries.

Answer 63

False ## Footnote Guidelines vary significantly between countries.

Question 64

What type of data can be requested for access according to the data sharing section?

Answer 64

De-identified participant data ## Footnote This includes efficacy, toxicity, and adherence variables.

Question 65

List some contributors to the trial design.

Answer 65

* MM * JAL * AH * GE * PD ## Footnote These contributors played key roles in developing the trial design.

Question 66

What are the grant numbers that funded the trial?

Answer 66

C37815/A12832 and CTUQQR-Dec22/100009 ## Footnote Funding was provided by Cancer Research UK.

Question 67

Fill in the blank: _____ is the FDA-approved drug combined with chemoradiotherapy for cervical cancer.

Answer 67

Pembrolizumab ## Footnote This approval is for FIGO 2014 stage III-IVA cervical cancer.

Question 68

What is the role of AH and SV in the trial?

Answer 68

Conducted statistical analysis and verified underlying data ## Footnote They ensured the integrity of the data reported in the manuscript.

Question 69

What type of study was conducted to assess the feasibility and safety of induction chemotherapy?

Answer 69

A single-arm phase II clinical trial ## Footnote This trial focused on locally advanced cervical cancer.

Question 70

True or False: All authors declared competing interests.

Answer 70

False ## Footnote All other authors besides GE, JAL, MM, and AH declared no competing interests.

Question 71

What is the purpose of the INTERLACE Trial Management Group?

Answer 71

To review proposals for data access requests ## Footnote They will establish a data sharing agreement if accepted.

Question 72

What is the significance of the CALLA trial mentioned?

Answer 72

It compares durvalumab versus placebo with chemoradiotherapy ## Footnote This is a randomised, double-blind, phase 3 trial for locally advanced cervical cancer.