Management of testicular tumours in patients with undescended testes- a challenging but rewarding task: experience from a tertiary care cancer centre in India.

Objective: Primary objective: To study patients' clinical profile and outcomes with germ cell tumours developing in undescended testes. Materials and methods: Case records of patients enlisted in the prospectively maintained 'testicular cancer database' at our tertiary cancer care hospital from 2014 to 2019 were retrospectively reviewed. Any patient who presented with testicular germ cell tumour with a documented history/diagnosis of undescended testes, whether surgically corrected or not, was considered for this study. The patients were managed along the standard lines of treatment for testicular cancer. We evaluated clinical features, difficulties and delays in diagnosis and complexities in management. We evaluated event-free survival (EFS) and overall survival (OS) using the Kaplan-Meier Method. Results: Fifty-four patients were identified from our database. The mean age was 32.4 years (median age 32, range: 15-56 years). Seventeen (31.4%) had developed cancer in orchidopexy testes, and 37 (68.6%) presented with testicular cancer in uncorrected cryptorchid testes. The median age at orchidopexy was 13.5 years (range: 2-32 years). The median time from symptom onset to diagnosis was 2 months (1-36 months). There was a delay in the initiation of treatment of more than 1 month in 13 patients, with the longest delay being 4 months. Two patients were initially misdiagnosed as gastrointestinal tumours. Thirty-two (59.25%) patients had seminoma, and 22 (40.7%) patients had non-seminomatous germ cell tumours (NSGCT). Nineteen patients had metastatic disease at presentation. Thirty (55.5%) patients underwent orchidectomy upfront while in 22 (40.7%) patients, orchidectomy was done after chemotherapy. The surgical approach included high inguinal orchidectomy, exploratory laparotomy or laparoscopic surgery per the clinical situation. Post-operative chemotherapy was offered as clinically indicated. At a median follow-up of 66 months (95% CI: 51-76), there were four relapses (all NSGCT) and one death. The 5-year EFS was 90.7% (95% CI: 82.9-98.7). The 5-year OS was 96.3% (95% CI: 91.2-100). Conclusions: The tumours in undescended testes, particularly those without prior orchiopexy, often presented late and with bulky masses, requiring complex multidisciplinary management. Despite the complexity and challenges, our patient's OS and EFS matched that of patients with tumours in normally descended testes. Orchiopexy may help in earlier detection. In the first such series from India, we show that testicular tumours in the cryptorchid are also as curable as the germ cell tumours developing in the descended testis.A multidisciplinary disease management group with expertise in managing complex cases is crucial for a favourable outcome in these groups of patients. We also found that orchiopexy done even later in life confers an advantage in terms of early detection in a subsequently developing testicular tumour.

Cancer care continuum at a tertiary care centre in India during the Covid-19 pandemic and nationwide lockdown: Healthcare delivery through telemedicine.

Background The Covid-19 pandemic and subsequent lockdown in India caused disruptions in cancer treatment due to the restriction on movement of patients. We aimed to maintain continuity in cancer treatment during the lockdown through teleconsultations. We tried to reach out to our patients using telephonic consultations by establishing a Teleconsult Centre facility run by a team of doctors and patient navigators. Methods We telephonically contacted all patients who had outpatient appointments from 23 March to 30 April 2020 at our centre through the Teleconsult Centre to understand their current circumstances, feasibility of follow-up, local resources and offered best possible alternatives to continue cancer treatment, if required. Results Of the 2686 patients scheduled for follow-up during this period, we could contact 1783 patients in 9 working days. Through teleconsultations, we could defer follow-ups of 1034 patients (57.99%, 95% confidence interval [CI] 55.6%-60.3%), thus reducing the need for patients to travel to the hospital. Change in systemic therapy was made in 75 patients (4.2%, 95% CI 3.3%-5.2%) as per the requirements and available resources. Symptoms suggestive of disease progression were picked up in 12 patients (0.67%, 95% CI 0.35%-1.17%), who were advised to meet local physicians. Conclusion Our study suggests that the majority of patients on follow-up can be managed with teleconsultation in times of crisis. Teleconsultation has the potential of being one of the standard methods of patient follow-up even during periods of normalcy.

Second-line therapy in testicular germ cell tumours: results from a tertiary cancer care centre in India.

Background: Malignant testicular neoplasms constitute about 1% of all cancers in males. This is one of the most common tumours in adolescents and young adult males. After the introduction of cisplatin-based chemotherapy, the survival of germ cell tumour patients, even those with poor prognostic risk factors, has significantly improved over the years. Second-line chemotherapy in patients who have progressed over the first-line cisplatin-based chemotherapy has shown convincing 5 years of overall survival (OS). Methodology: This study is a retrospective analysis of testicular cancer patients from 2014 to 2020 who have received salvage chemotherapy treatment at Tata Memorial Centre. Patient demographics, tumour characteristics and treatment details were recorded in a specific format, and progression-free survival and OS were analysed along with response to therapy. Results: A total of 46 testicular cancer patients from 2014 to 2020, who received second-line chemotherapy, were analysed from the database maintained at our hospital. The median age at diagnosis was 29.5 (18-60) years. Most of the patients (30, 65.2%) presented with lung metastasis and 11 (23.9%) patients with liver metastasis. Most of the patients (21, 45.6%) received vinblastine, ifosfamide and cisplatin, whereas 13 (28.2%) patients received paclitaxel, ifosfamide and cisplatin regimen and 7 (15.2%) patients received GemOx regimen as the second-line chemotherapy. Median OS was observed to be 33.97 months and median progression-free survival was 29.01 months. Conclusion: Second-line chemotherapy in testicular germ cell tumours can result in long-term disease control and all patients who are fit to tolerate second-line therapy should be offered it. Patients with relapsed seminoma did better than relapsed non-seminomatous germ cell tumours.

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. FUNDING: Tata Memorial Center Research Administration Council. TRANSLATIONS: For the Hindi, Marathi, Gujarati, Kannada, Malayalam, Telugu, Oriya, Bengali, and Punjabi translations of the abstract see Supplementary Materials section.

Reverse swing-M, phase 1 study of repurposing mebendazole in recurrent high-grade glioma.

BACKGROUND: Relapsed high-grade glioma has dismal outcomes. Mebendazole has shown promising activity against glioma in in-vitro and in-vivo studies. Hence, we undertook a phase 1 study to repurpose mebendazole in the treatment of glioblastoma. METHODS: We conducted a phase 1 study (accelerated titrated design 4) of mebendazole in patients with recurrent glioblastoma (GBM). Patients eligible for re-irradiation were enrolled in arm A1 (radiation with concurrent temozolomide 75 mg/m2 daily during the course of radiation+mebendazole) while patients who were ineligible were enrolled in either arm B1 (CCNU 110 mg/m2 day 1, every 6 weekly + mebendazole) or arm C1 (temozolomide 200 mg/m2 day 1-5, every 4 weekly + mebendazole). The primary endpoint of phase 1 was to identify the MTD of mebendazole in each combination. FINDINGS: 11 patients were enrolled in the whole study. MTD of mebendazole was not reached in arm A1 and C1 and hence the recommended dose for phase 2 was 1600 mg TDS (4800 mg) per day. The MTD of mebendazole in combination with CCNU was 1600 mg TDS (4800 mg) per day and the dose recommended for phase 2 was 800 mg TDS (2400 mg) per day. The three most common adverse events seen in the study were anemia (n = 9, 81.8%), nausea (n = 7, 63.6%), and fatigue (n = 6, 55.5%). INTERPRETATION: The recommended phase 2 dose of mebendazole is 1600 mg TDS with temozolomide and temozolomide-radiation combination while the dose of 800 mg TDS needs to be used with single-agent CCNU.

Presentation and Outcomes with First-Line Chemotherapy in Advanced Cholangiocarcinomas-A Relatively Rare Component of Biliary Tract Cancers in India.

Background Biliary tract cancers (BTCs) are a rare group of cancers with limited data with respect to advanced unresectable cholangiocarcinoma (CCA). Materials and Methods The study is a retrospective study of patients with advanced unresectable/metastatic CCA, who received first-line palliative chemotherapy (CT1) from January 2014 to March 2019 at the Tata Memorial Hospital, Mumbai. Baseline clinical characteristics, chemotherapeutic regimens, and toxicities were evaluated. Results One hundred and forty patients satisfied criteria for evaluation. Median age of the entire cohort was 57 years (range: 32-80). There were 87 patients (62.1%) with intrahepatic CCA, 35 patients (25%) with perihilar CCA, and 14 patients (10%) with distal CCA. One hundred and twelve patients (80%) had metastatic disease at presentation. Commonest CT1 regimens were gemcitabine-cisplatin (GC) in 89 patients (63.5%) and gemcitabine-oxaliplatin (GO) in 34 patients (24.3%). Sixty-three patients (45%) received second-line chemotherapy. With a median follow-up of 27 months, median progression-free survival for the entire cohort was 7.56 months (95% confidence interval [CI]: 6.23-8.88), and median OS was 12.16 months (95% CI: 10.08-14.24). Common chemotherapy-related grade 3/4 side effects included vomiting in 25 patients (17.9%), diarrhea in 23 patients (16.4%), and thrombocytopenia in 22 patients (15.7%). Conclusion The current study in advanced CCAs is the largest of its nature from India. The common regimens used as first line were GC and GO. Tolerance and overall survival appear similar to previously published data.

Randomized phase 3 open label study of quality of life of patients on Pemetrexed versus Erlotinib as maintenance therapy for advanced non squamous non EGFR mutated non small cell lung cancer.

Background: We planned to compare pemetrexed maintenance with erlotinib maintenance in non squamous non Epidermal Growth Factor Receptor (EGFR) mutated non small cell lung cancer (NSCLC). The null hypothesis for this study was that there would be no difference in quality of life (QOL) between pemetrexed and erlotinib maintenance. Results: The QL2 scores at 3 months were 63.35 (SD 24.99) in pemetrexed arm and 63.01(SD 23.04) in erlotinib arm (p-0.793). Except in 1 domain, the scores were statistically similar between the 2 arms. In the domain of diarrhea, the score was higher as expected in the erlotinib arm (p-0.048). The median progression free survival was 4.5 months (95%CI 4.1-4.9 months) in pemetrexed arm versus 4.5 months (95%CI 3.8-5.2 months) in erlotinib arm (p-0.94). The median overall survival was 16.6 months (15.2-17.9 months) in pemetrexed arm versus 18.3 months (95% CI 13.75-22.91 months) in erlotinib arm (p-0.49). Methods: The study was an open label, single centre, parallel, phase 3 randomized study with 1:1 randomization between maintenance pemetrexed arm and erlotinib arm. Adult patients (age > or = 18 years), with non squamous EGFR mutation, treated with first line palliative therapy, with non progressive disease post 4-6 cycles of pemetrexed-carboplatin were randomized. Primary outcome was change in the score of QOL (Global health status {QL2}) at 3 months. We estimated that with 200 patients, the study had 80% power to detect a significant difference between the two groups in the change in the global health status score at 3 months with an alpha error of 5%, with an effect size of 0.3 SD. Conclusions: Maintenance pemetrexed post pemetrexed-platinum chemotherapy fails to improve QOL or time to event outcomes over maintenance erlotinib in EGFR mutation negative NSCLC.

Phase I/II Study of Palliative Triple Metronomic Chemotherapy in Platinum-Refractory/Early-Failure Oral Cancer.

PURPOSE: Platinum-resistant oral cancer has a dismal outcome with limited treatment options. We conducted a phase I/II study to identify the optimal biologic dose (OBD) of methotrexate when given along with erlotinib and celecoxib and to assess the efficacy of this three-drug regimen in advanced oral cancer. METHODS: Patients with platinum-resistant or early-failure squamous cell carcinoma of the oral cavity were eligible for this study. They were orally administered erlotinib 150 mg once per day, celecoxib 200 mg twice per day, and methotrexate per week. The primary end point of phase I was to determine the OBD of methotrexate, and that of phase II was to determine the 3-month progression-free survival. The OBD of methotrexate was determined on the basis of the clinical benefit rate at 2 months and circulating endothelial cell level at day 8, using a de-escalation model. Pharmacokinetic evaluation was performed during phase I. Phase II consisted of an expansion cohort of 76 patients. RESULTS: Fifteen patients were recruited in phase I, and 9 mg/m2 methotrexate was identified as the OBD. A total of 91 patients were recruited, and the median follow-up was 6.8 months (range, 0 to 16.8 months). The 3-month progression-free survival rate was 71.1% (95% CI, 60.5% to 79.3%), the 6-month overall survival rate was 61.2% (95% CI, 49.2% to 67.8%), and the response rate was 42.9% (95% CI, 33.2% to 53.1%; n = 39). The mean Functional Assessment of Cancer Therapy-Head and Neck Trial Outcome Index score at day 8 was improved by 6.1 units (standard deviation, 13.6 units) and was maintained around this magnitude (P = .001). CONCLUSION: Triple oral metronomic chemotherapy with erlotinib, methotrexate, and celecoxib is efficacious in platinum-refractory oral cavity cancers and represents a new therapeutic option in patients with poor prognosis.

Palliative chemotherapy in carcinoma nasopharynx.

INTRODUCTION: Nasopharyngeal carcinoma is a rare malignancy. We conducted an audit of systemic therapies received in palliative setting in carcinoma nasopharynx and studied their outcomes. METHODS: Patients who underwent first-line palliative systemic chemotherapy between January 2014 and April 2017 for carcinoma nasopharynx at the department of medical oncology at authors' institute were selected for this analysis. Toxicities, responses, progression-free survival (PFS), and overall survival (OS) were analyzed. In addition, a Quality-Adjusted Time without Symptoms or Toxicity analysis with threshold utility analysis was performed. RESULTS: Fifty-one patients were included in this analysis. The indication of palliative chemotherapy was locoregionally recurrent disease in 25 (49.0%) patients and metastatic disease in 26 (51.0%) patients. The overall response rate was 62.0% (n = 33). The median PFS was 225 days (95% confidence interval [CI]: 164-274 days) and median OS was 513 days (95% CI: 286-931 days). The restricted mean TOX state duration was 2.6 days (95% CI: 0.3-4.9), restricted mean TWiST duration was 219.2 days (95% CI: 184.0-254.4), and restricted mean REL duration was 74.3 days (95% CI: 38.1-110.4). CONCLUSION: Systemic cytotoxic therapy in nasopharyngeal cancers is associated with high response rates and clinically meaningful PFS; with low duration of time spent in adverse events.

Osteosarcoma journey over two decades in India: Small steps, big changes.

BACKGROUND: The management of osteosarcoma is challenging especially in lower-income and middle-income countries, and there is an unmet need to evolve efficient and sustainable chemotherapy regimens. METHODS: We compared the outcomes in nonmetastatic osteosarcoma patients treated with three sequential non-high-dose methotrexate-based combination chemotherapy protocols at a single tertiary care center over two decades. The first protocol, OGS-99, involved dose-intense, alternating dyads of three drugs: doxorubicin (Dox), cisplatin (CDDP), and ifosfamide (Ifo). The second protocol, OGS-99 enhanced, included OGS-99 drugs with etoposide and enhanced supportive care. The OGS-12 protocol involved dose-dense administration of eight sequential dyads of Dox, CDDP and Ifo, universal growth factor prophylaxis and targeted nutritional support. Event-free survival (EFS), overall survival (OS), and toxicity were reported using a retrospective chart review in the OGS-99 and OGS-99 enhanced protocols and prospectively in the OGS-12 protocol. RESULTS: A total of 41, 94, and 385 treatment-naïve, consecutive, nonmetastatic patients with extremity osteosarcoma were treated with the OGS-99 (2000-2005), OGS-99 enhanced (2010), and OGS-12 (2011-2016), respectively. At a median follow-up of 19, 86, and 39 months, the five-year EFS rates were 38%, 50%, and 62% in the OGS-99, OGS-99 enhanced, and OGS-12, respectively. The corresponding rates of five-year OS were nonevaluable, 60% and 77%, respectively, with acceptable rates of grade 3-4 toxicities: febrile neutropenia (40%), thrombocytopenia (36%), anemia (51%), and 1% deaths related to toxicity. CONCLUSIONS: Sequential selection of an intelligent, dose-dense chemotherapy regimen together with enhanced supportive care resulted in marked improvement in outcomes of nonmetastatic osteosarcoma and this "small steps-big changes" model deserves wider recognition and usage.

A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer.

BACKGROUND: Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. METHODS: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. RESULTS: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). CONCLUSIONS: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.

Modified 5-fluorouracil/leucovorin/irinotecan as a feasible and efficacious second-line chemotherapeutic regimen in advanced gastric cancers.

BACKGROUND: Modified 5-fluorouracil/leucovorin/irinotecan (mFOLFIRI) is a commonly used combination second-line chemotherapeutic regimen in advanced gastric cancer (AGC). MATERIALS AND METHODS: Patients diagnosed with AGC, receiving biweekly mFOLFIRI between July 2013 and June 2016, as second-line chemotherapy were retrospectively analyzed for tolerance, prognostic factors, event-free survival (EFS), and overall survival (OS). RESULTS: Overall, 91 patients were administered a median of 6 cycles of therapy. Response rate was 29.7% and clinical benefit rate was 57.2%. With a median follow-up of 11.5 months, median EFS was 3.98 months (95% confidence interval [CI]: 2.54-5.41) and median OS was 7.73 months (95% CI: 5.30-10.15). Common Grade 3 and Grade 4 adverse events were neutropenia (18.7%), febrile neutropenia (9.9%), thrombocytopenia (7.7%), and vomiting (4.4%). Nearly 33% of patients required dose modification during therapy. CONCLUSIONS: mFOLFIRI regimen as a second-line therapy in AGCs appears feasible and efficacious in clinical practice.

Outcomes in Treatment-Naïve Patients With Metastatic Extremity Osteosarcoma Treated With OGS-12, a Novel Non-High-Dose Methotrexate-Based, Dose-Dense Combination Chemotherapy, in a Tertiary Care Cancer Center.

PURPOSE: Metastatic osteosarcoma is largely treated with high-dose methotrexate (HDMTX)-based therapy, especially in the pediatric population. This mandates complex pharmacokinetic monitoring in a costly inpatient setting to mitigate unpredictable serious toxicities. Hence, a non-HDMTX-based regimen is worth exploring, especially in India and low- and middle-income countries. MATERIALS AND METHODS: All consecutive treatment-naïve patients with metastatic osteosarcoma were prospectively treated on the novel OGS-12 protocol consisting of sequential doublets of doxorubicin, cisplatin, and ifosfamide. Four cycles were administered as neoadjuvant therapy followed by planned curative intent surgery and metastasectomy when feasible, followed by four cycles of adjuvant chemotherapy. Baseline characteristics, histologic response, event-free survival (EFS), overall survival (OS), and toxicity data were prospectively collected. RESULTS: Three hundred seventeen patients were enrolled onto the OGS-12 protocol from 2011 to 2014, of whom 80 (25%) had metastatic disease; median age was 17 years. The majority of patients were nutritionally challenged with high-risk features. At presentation, 83% of patients (66 patients) had lung metastases. After neoadjuvant chemotherapy, 57% of patients were histologically good responders. Four-year EFS and OS rates were 24% and 27%, respectively, in the intent-to-treat population and 27% and 29%, respectively, in the per-protocol analysis. Significant grade 3 or 4 toxicities were febrile neutropenia (51%), thrombocytopenia (36%), and anemia (54%). Histologic response was an independent predictor for EFS and OS in patients who underwent surgery. Surgical intervention was found to be significant for survival in univariable analysis. CONCLUSION: The novel, low-cost, non-HDMTX-based, dose-dense OGS-12 regimen has shown comparable outcomes to international standards in metastatic osteosarcomas and is worthy of wider clinical application. An aggressive multimodality approach may result in long-term survival in a select group of patients and, hence, is worth considering.

Clinical outcomes with MRI-guided image-based brachytherapy in cervical cancer: An institutional experience.

PURPOSE: To evaluate the long-term disease control and toxicity to the organs at risk after dose-escalated image-based adaptive brachytherapy (BT) in cervical cancer. METHODS AND MATERIALS: Sixty patients of cervical cancer were treated with external radiotherapy 46 Gy in 23 fractions with weekly cisplatin and MRI-guided BT 7 Gy × 4 fractions with a minimum dose of 85.7 Gy (EQD2) to the high-risk clinical target volume (HRCTV). The BT dose was initially prescribed to point A and plans were optimized to ensure coverage of both point A and HRCTV while maintaining doses to the organs at risk within the recommended constraints. Patients were followed up clinically every three months for the first two years and six months thereafter. Toxicity scoring for urinary and bowel symptoms was done using CTCAE version 3.0. RESULTS: The mean doses to the point A and D90 HRCTV were 85.5 (±2.75) Gy and 98.4 (±9.6) Gy EQD2 respectively. The mean 2 cc EQD2, the bladder, rectum, and sigmoid were 90.6 Gy, 70.2 Gy, and 74.2 Gy respectively. The overall survival at a median followup of 49.8 months was 91.66%. Six (10%) patients developed grade 3 gastrointestinal toxicity. One patient developed grade 3 bladder toxicity. The incidence of bladder, rectal, and sigmoid toxicity increased significantly with doses >85 Gy, 66 Gy, and >71 Gy EQD2 respectively. CONCLUSIONS: While the incidence of grade 3-4 toxicity was low (8.3% for gastrointestinal toxicity and 1.6% for bladder), the threshold for development of grade 1-2 bladder and rectal toxicity was lower than the doses recommended by the GEC-ESTRO group. By adhering to volume-based prescriptions, there is scope of further reduction in toxicity to organs at risk.

Outcomes in non-metastatic treatment naive extremity osteosarcoma patients treated with a novel non-high dosemethotrexate-based, dose-dense combination chemotherapy regimen 'OGS-12'.

PURPOSE: High-dose methotrexate (HDMTX)-based regimens are widely used in osteosarcoma. However, mandatory in-patient treatment with complex pharmacokinetic monitoring requirement precludes its use, especially in resource-constrained settings of low- and middle-income countries (LMICs). METHODS: All treatment naive consecutive patients of osteosarcoma were prospectively treated on a novel institutional regimen (named OGS-12) comprising of eight sequential doublets of the following drugs: doxorubicin, cisplatin and ifosfamide in four courses each, given in the neoadjuvant and adjuvant settings. Data were prospectively collected on baseline characteristics, histological response to neoadjuvant chemotherapy (NACT), toxicity, event-free survival (EFS) and overall survival (OS). RESULTS: Between 2011 and 2014, 317 treatment naive patients with extremity osteosarcoma were seen, of whom 237 (75%) were non-metastatic. Majority had high tumour burden, with mean tumour size of 10.45 cm, high serum lactate dehydrogenase (LDH) and serum alkaline phosphatase (SAP) in 71% and 88% respectively. A significant number (34%) were nutritionally challenged. Two-hundred ten of 237 patients were analysable for histological response of which 58% had good response (viable cells ≤10%). At the median follow-up of 34.31 (2-60) months, in intention-to-treat (ITT) analysis, the 5-year EFS and OS were 56% and 75% respectively; the same were 60% and 80% in per-protocol analysis. There was febrile neutropenia (FN) in 56%, grade 3/4 thrombocytopaenia in 22% and anaemia in 47% with two chemotoxic deaths. Ten percent of the patients had grade 3/4 diarrhoea and stomatitis and one patient developed grade 4 acute kidney injury requiring dialysis. Baseline SAP (per-protocol) for EFS and performance status (ITT) for OS were found to be independent variables. Histological response was an independent predictor for EFS and OS in both the analyses. CONCLUSIONS: In treatment naive patients with non-metastatic osteosarcoma, OGS-12 protocol, a dose-dense, non-HDMTX-based, novel, economic and easy to administer regimen produces comparable outcomes to international standards, with acceptable toxicity and is worthy of wider clinical application.

Multiple localized metachronous recurrences in a patient of colon cancer and therapeutic controversies in stage II colon cancer.

Recurrences of colon cancer occurs in 30-40% of the patients after successful initial therapy and most commonly occur at distant sites like liver, lungs and lymph nodes. Here we present a patient who presented with localized metachronous recurrences of colonic cancer over a span of 20 years; each time presenting in stage II and was successfully salvaged with surgery followed by adjuvant chemotherapy. Recurrences were detected on screening colonoscopy at each instance. We also discuss the role of adjuvant chemotherapy in stage II colon cancer, current indications of chemotherapy and the role of gene assays. The independent survival benefit conferred by screening treated patients with colon cancer is also highlighted.

Evaluation of neuropathic pain occurring after high-dose-rate interstitial brachytherapy of oral tongue.

PURPOSE: To recognize neuropathic pain as a complication of high-dose-rate (HDR) interstitial brachytherapy of oral tongue and to evaluate the possible causes of neuropathy. MATERIAL AND METHODS: Twenty one patients who underwent interstitial brachytherapy for early cancer of oral tongue were evaluated. The patients either underwent primary brachytherapy (42-48 Gy at 3-4 Gy/fraction) or a boost (18-24 Gy at 3 Gy/fraction) after external radiation to 40 Gy. Lingual nerve was the nerve concerned and the sublingual space (SLS) was contoured as its surrogate. Dosimetric parameters were correlated with onset of pain. RESULTS: Ten patients out of 21 (47.61%) developed painful neuropathy. Five patients of six (5/6) who underwent primary brachytherapy developed neuropathy. Five out of 15 (5/15) patients who underwent brachytherapy as a boost developed neuropathy. The patients who underwent primary brachytherapy were ten times more likely to develop neuropathy. Among the patients receiving boost treatment, the equivalent dose at 2 Gy/fraction (EQD2) to 2 cc of SLS was higher (39.25 Gy) in the patients who developed pain compared to those without pain (10.29 Gy). CONCLUSIONS: This is the first report to recognize neuropathic pain as a complication of HDR brachytherapy of oral tongue. Patients undergoing primary brachytherapy were more likely to develop pain. Among other factors like dose to SLS, number of catheters, size of the primary tumor, and the dose rate, only dose to 2 cc of the SLS correlated with onset of pain. The SLS (containing the lingual nerve) may be considered an organ at risk to prevent the occurrence of this complication.

Mucinous adenocarcinoma of the rectum: a poor candidate for neo-adjuvant chemoradiation?

BACKGROUND: Mucinous adenocarcinoma (MA) is a distinct pathological entity associated with poor outcome. Due to different biological behavior, the response to neoadjuvant chemo-radiation (NACRT) may be inferior compared to non-mucinous tumours. In this study we compare the pathological response of mucinous tumours after NACRT. METHODS: A total of 183 patients who underwent NACRT for rectal cancer were classified as mucinous and non-MAs. The dose of radiation was 45 Gy (at 1.8 Gy per fraction) delivered over five weeks with weekly 5-flourouracil (5-FU) (325 mg/m(2)) and leucovorin (20 mg/m(2)). After surgery, the pathological specimens were evaluated and staged. The data are reported as descriptive statistics and chi-square test used to determine difference in proportions. RESULTS: The two varieties were comparable on the basis of the computed tomography (CT) scan in terms of tumour size and lymph node metastasis. However in terms of pathological response, it was seen that there was a higher incidence of pT4 tumours (73.5% vs. 10.7%), margin positivity (11.7% vs. 2.3%) and advanced nodal disease pN2 (29.4% vs. 9.3%) in mucinous and non-mucinous tumours respectively. CONCLUSIONS: MA of the rectum show a poor response to NACRT as seen in terms of larger residual tumours, higher incidence of margin positivity, and greater residual nodal disease. Also they showed higher incidence of peritoneal and distant dissemination during NACRT. The role of NACRT in mucinous carcinoma of the rectum is of questionable benefit and needs to be examined in prospective trials.