Impact of consolidation chemotherapy in poor responders to neoadjuvant radiation therapy: magnetic resonance imaging–based clinical-radiological correlation in high-risk rectal cancers

Purpose The current study was conducted to examine the role of consolidation chemotherapy after neoadjuvant radiation therapy (NART) in decreasing the involvement of the mesorectal fascia (MRF) in high-risk locally advanced rectal cancers (LARCs). Methods In total, 46 patients who received consolidation chemotherapy after NART due to persistent MRF involvement were identified from a database. A team of 2 radiologists, blinded to the clinical data, studied sequential magnetic resonance imaging (MRI) scans to assess the tumor response and then predict a surgical plan. This prediction was then correlated with the actual procedure conducted as well as histopathological details to assess the impact of consolidation chemotherapy. Results The comparison of MRI-based parameters of sequential images showed significant downstaging of T2 signal intensity, tumor height, MRF involvement, diffusion restriction, and N category between sequential MRIs (P0.3) was observed for only T2 signal intensity and diffusion restriction on diffusion-weighted imaging. No clinically relevant changes occurred in the remaining parameters; thus, no change was noted in the extent of surgery predicted by MRI. Weak agreement (Cohen κ coefficient, 0.375) and correlation (Spearman rank coefficient, 0.231) were found between MRI-predicted surgery and the actual procedure performed. The comparison of MRI-based and pathological tumor response grading also showed a poor correlation. Conclusion Evidence is lacking regarding the use of consolidation chemotherapy in reducing MRF involvement in LARCs. The benefit of additional chemotherapy after NART in decreasing the extent of planned surgery by reducing margin involvement requires prospective research

Evaluation of an Objective MRI-Based Tumor Regression Grade (mrTRG) Score and a Subjective Likert Score for Assessing Treatment Response in Locally Advanced Rectal Cancers—A Retrospective Study

Purpose: Magnetic resonance imaging (MRI) with the help of MRI-based tumor regression grade (mrTRG) score has been used as a tool to predict pathological tumor regression grade (pTRG) in patients of rectal cancer post-neoadjuvant chemoradiation. Our study aims to evaluate the ability of MRI in assessing treatment response comparing an objective mrTRG score and a subjective Likert score, with a focus on the ability to predict pathologic complete response (pCR)

Low-cost oral metronomic chemotherapy versus intravenous cisplatin in patients with recurrent, metastatic, inoperable head and neck carcinoma:an open-label, parallel-group, non-inferiority, randomised, phase 3 trial

BACKGROUND: Regimens for palliation in patients with head and neck cancer recommended by the US National Comprehensive Cancer Network (NCCN) have low applicability (less than 1–3%) in low-income and middle-income countries (LMICs) because of their cost. In a previous phase 2 study, patients with head and neck cancer who received metronomic chemotherapy had better outcomes when compared with those who received intravenous cisplatin, which is commonly used as the standard of care in LMICs. We aimed to do a phase 3 study to substantiate these findings.METHODS: We did an open-label, parallel-group, non-inferiority, randomised, phase 3 trial at the Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India. We enrolled adult patients (aged 18–70 years) who planned to receive palliative systemic treatment for relapsed, recurrent, or newly diagnosed squamous cell carcinoma of the head and neck, and who had an Eastern Cooperative Oncology Group performance status score of 0–1 and measurable disease, as defined by the Response Evaluation Criteria In Solid Tumors. We randomly assigned (1:1) participants to receive either oral metronomic chemotherapy, consisting of 15 mg/m² methotrexate once per week plus 200 mg celecoxib twice per day until disease progression or until the development of intolerable side-effects, or 75 mg/m² intravenous cisplatin once every 3 weeks for six cycles. Randomisation was done by use of a computer-generated randomisation sequence, with a block size of four, and patients were stratified by primary tumour site and previous cancer-directed treatment. The primary endpoint was median overall survival. Assuming that 6-month overall survival in the intravenous cisplatin group would be 40%, a non-inferiority margin of 13% was defined. Both intention-to-treat and per-protocol analyses were done. All patients who completed at least one cycle of the assigned treatment were included in the safety analysis. This trial is registered with the Clinical Trials Registry-India, CTRI/2015/11/006388, and is completed.FINDINGS: Between May 16, 2016, and Jan 17, 2020, 422 patients were randomly assigned: 213 to the oral metronomic chemotherapy group and 209 to the intravenous cisplatin group. All 422 patients were included in the intention-to-treat analysis, and 418 patients (211 in the oral metronomic chemotherapy group and 207 in the intravenous cisplatin group) were included in the per-protocol analysis. At a median follow-up of 15·73 months, median overall survival in the intention-to-treat analysis population was 7·5 months (IQR 4·6–12·6) in the oral metronomic chemotherapy group compared with 6·1 months (3·2–9·6) in the intravenous cisplatin group (unadjusted HR for death 0·773 [95% CI 0·615–0·97, p=0·026]). In the per-protocol analysis population, median overall survival was 7·5 months (4·7–12·8) in the oral metronomic chemotherapy group and 6·1 months (3·4–9·6) in the intravenous cisplatin group (unadjusted HR for death 0·775 [95% CI 0·616–0·974, p=0·029]). Grade 3 or higher adverse events were observed in 37 (19%) of 196 patients in the oral metronomic chemotherapy group versus 61 (30%) of 202 patients in the intravenous cisplatin group (p=0·01).INTERPRETATION: Oral metronomic chemotherapy is non-inferior to intravenous cisplatin with respect to overall survival in head and neck cancer in the palliative setting, and is associated with fewer adverse events. It therefore represents a new alternative standard of care if current NCCN-approved options for palliative therapy are not feasible

Low-cost oral metronomic chemotherapy versus intravenous cisplatin in patients with recurrent, metastatic, inoperable head and neck carcinoma:an open-label, parallel-group, non-inferiority, randomised, phase 3 trial

BACKGROUND: Regimens for palliation in patients with head and neck cancer recommended by the US National Comprehensive Cancer Network (NCCN) have low applicability (less than 1–3%) in low-income and middle-income countries (LMICs) because of their cost. In a previous phase 2 study, patients with head and neck cancer who received metronomic chemotherapy had better outcomes when compared with those who received intravenous cisplatin, which is commonly used as the standard of care in LMICs. We aimed to do a phase 3 study to substantiate these findings.METHODS: We did an open-label, parallel-group, non-inferiority, randomised, phase 3 trial at the Department of Medical Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, India. We enrolled adult patients (aged 18–70 years) who planned to receive palliative systemic treatment for relapsed, recurrent, or newly diagnosed squamous cell carcinoma of the head and neck, and who had an Eastern Cooperative Oncology Group performance status score of 0–1 and measurable disease, as defined by the Response Evaluation Criteria In Solid Tumors. We randomly assigned (1:1) participants to receive either oral metronomic chemotherapy, consisting of 15 mg/m² methotrexate once per week plus 200 mg celecoxib twice per day until disease progression or until the development of intolerable side-effects, or 75 mg/m² intravenous cisplatin once every 3 weeks for six cycles. Randomisation was done by use of a computer-generated randomisation sequence, with a block size of four, and patients were stratified by primary tumour site and previous cancer-directed treatment. The primary endpoint was median overall survival. Assuming that 6-month overall survival in the intravenous cisplatin group would be 40%, a non-inferiority margin of 13% was defined. Both intention-to-treat and per-protocol analyses were done. All patients who completed at least one cycle of the assigned treatment were included in the safety analysis. This trial is registered with the Clinical Trials Registry-India, CTRI/2015/11/006388, and is completed.FINDINGS: Between May 16, 2016, and Jan 17, 2020, 422 patients were randomly assigned: 213 to the oral metronomic chemotherapy group and 209 to the intravenous cisplatin group. All 422 patients were included in the intention-to-treat analysis, and 418 patients (211 in the oral metronomic chemotherapy group and 207 in the intravenous cisplatin group) were included in the per-protocol analysis. At a median follow-up of 15·73 months, median overall survival in the intention-to-treat analysis population was 7·5 months (IQR 4·6–12·6) in the oral metronomic chemotherapy group compared with 6·1 months (3·2–9·6) in the intravenous cisplatin group (unadjusted HR for death 0·773 [95% CI 0·615–0·97, p=0·026]). In the per-protocol analysis population, median overall survival was 7·5 months (4·7–12·8) in the oral metronomic chemotherapy group and 6·1 months (3·4–9·6) in the intravenous cisplatin group (unadjusted HR for death 0·775 [95% CI 0·616–0·974, p=0·029]). Grade 3 or higher adverse events were observed in 37 (19%) of 196 patients in the oral metronomic chemotherapy group versus 61 (30%) of 202 patients in the intravenous cisplatin group (p=0·01).INTERPRETATION: Oral metronomic chemotherapy is non-inferior to intravenous cisplatin with respect to overall survival in head and neck cancer in the palliative setting, and is associated with fewer adverse events. It therefore represents a new alternative standard of care if current NCCN-approved options for palliative therapy are not feasible