Oncofertility and Pregnancy in Adolescent and Young Adult Cancers: Physicians' Knowledge and Preferences in India.

PURPOSE: The treatment outcomes of adolescent and young adult (AYA) cancers have improved with advanced oncology care. Hence, fertility preservation (FP) and post-therapy pregnancies (PTPs) become vital issues. MATERIALS AND METHODS: An online survey link with 17 questions regarding oncofertility and PTPs was circulated among oncologists to assess the knowledge, understand the oncofertility care patterns, and seek suggestions to improve oncofertility services. RESULTS: The median age of 179 respondents, predominantly medical oncologists (68.7%), was 37 years (IQR, 10; range, 29-74), working in academic centers (39%) having a median experience of 4 years (IQR, 4; range, 1-42); 23 (12.8%) had dedicated AYA cancer units. Although a quarter (19%-24%) of respondents discussed fertility issues in >90% of AYA patients with cancer, only a tenth (8%-11%) refer >90% for FP, with significantly higher (P < .05) discussions and referrals in males and by more experienced oncologists (P < .05). Forty-six (25.6%) were not well versed with international guidelines for FP. Most (122, 68.1%) oncologists knew about the referral path for semen cryopreservation; however, only 46% were knowledgeable about additional complex procedures. One hundred and ten (61.5%) oncologists never or rarely altered the systemic treatment for FP. Prominent barriers to FP were ignorance, lack of collaboration, and fear of delaying cancer treatment. Lead thrust areas identified to improve FP practices are education, and enhanced and affordable access to FP facilities. Seventy-four (41.3%) respondents knew about international guidelines for PTPs; however, only half (20%) of them often monitored fertility outcomes in survivors. Oncologists have conflicting opinions and uncertainties regarding pregnancy safety, assisted reproductive techniques, breastfeeding, and pregnancy outcomes among survivors. CONCLUSION: Oncologists are uncertain about the guidelines, FP practices, referral pathways, and PTPs. Multipronged approaches to improve awareness and provision for affordable oncofertility facilities are needed to enhance AYA cancer outcomes in India, which will be applicable to other low- and middle-income countries too.

Whole exome sequencing uncovers HRAS mutations as potential mediators of resistance to metronomic chemotherapy.

OBJECTIVES: The aim of this pilot study is to identify the genetic factors that contribute to the response of metronomic chemotherapy in head and neck squamous cell carcinoma (HNSCC) patients using whole-exome sequencing (WES). This study would facilitate the identification of predictive biomarkers, which would enable personalized treatment strategies and improve treatment outcomes for patients with HNSCC. MATERIALS AND METHODS: We have selected patients with recurrent head and neck cancer who underwent metronomic chemotherapy. Sequential tumor biopsies were collected from the patients at different stages of treatment to capture the genomic alterations and tumor evolution during metronomic chemotherapy and sequenced using WES. RESULTS: We identified several known HNSCC hallmark genes reported in COSMIC, including KMT2B, NOTCH1, FAT1, TP53, HRAS, CASP8, and CDKN2A. Copy number alteration analysis revealed amplifications and deletions in several oncogenic and tumor suppressor genes. COSMIC Mutational Signature 15 associated with defective DNA mismatch repair was enriched in 73% of HNSCC samples. Further, the comparison of genomic alterations between responders and non-responders identified HRAS gene uniquely mutated in non-responders that could potentially contribute to resistance against metronomic chemotherapy. DISCUSSION: Our findings corroborate the molecular heterogeneity of recurrent HNSCC tumors and establish an association between HRAS mutations and resistance to metronomic chemotherapy, suggesting HRAS as a potential therapeutic target. Combining HRAS inhibitors with metronomic regimens could improve treatment sensitivity in HRAS-mutated HNSCC patients. Further studies are needed to fully elucidate the genomic mechanisms underlying the response to metronomic chemotherapy.

Epidemiology of rare cancers in India and South Asian countries - remembering the forgotten.

Background: Rare cancers (RCs) are challenging to manage and are "forgotten cancers" though they collectively constitute a significant proportion of all cancers (∼20%). As a first step towards streamlining care, there is an unmet need to map the epidemiology of RCs in South Asian Association for Regional Collaboration (SAARC) countries. Methods: The authors collected data from 30 Population-Based Cancer Registries (PBCR) of India and the published national registries of Nepal, Bhutan and Sri Lanka (SL) and compared them with the standard RARECAREnet RC list. Findings: With the standard definition of crude incidence rates (CR) ≤6/100,0000 per population, 67.5%, 68.3%, 62.3% and 37% of all incident cancers qualify as RCs in India, Bhutan, Nepal and SL, respectively. An arbitrary cut-off CR ≤3 appears more appropriate with 43%, 39.5%, 51.8% and 17.2% of cancers identified as RCs, respectively, due to the lower cancer incidence.There are similarities and notable differences between the RC lists of the SAARC region with that of the European RC list. Oral cavity cancers are rare in Europe, while pancreas, rectum, urinary bladder and melanomas are common. In addition, uterine, colon and prostatic cancers are rare in India, Nepal and Bhutan. In SL, thyroid cancer is common. There are gender-related and regional differences in RC trends in the SAARC countries. Interpretation: There is an unmet need in SAARC nations to capture epidemiological nuances in rare cancers. Understanding the unique issues in the developing world may guide policymakers to adopt appropriate measures to improve RC care and tailor public health interventions. Funding: None.

Long-Term Outcomes in Survivors of Childhood Cancer: A 30-Year Experience From India.

PURPOSE: Despite an increasing number of survivors of childhood cancer (CCS) in low- and middle-income countries, survivorship care is in its nascent stages. We describe the spectrum of late effects seen, challenges faced, and lessons learnt over three decades of a late effects program in India. METHODS: We describe the demographics and profile of late effects of all CCS survivors enrolled in our After Completion of Treatment Clinic from February 5, 1991 (inception) to February 4, 2021. We analyzed the trends by the decade of diagnosis. RESULTS: There were 3,067 CCS survivors, the median age was 18 years (range, 3-57 years), and the median follow-up was 11 years (range, 2-46 years). Two thirds (62.4%) had either no or mild late effects, 480 (15.6%), 497 (16.2%), and 162 (5.3%) had grades 2, 3, and 4 late effects, with 67 deaths reported. Notable late effects were chronic viral hepatitis (7.8%), thyroid dysfunction (7.5%), other endocrine issues (13.6%), psychosocial issues (57%), neurocognitive impairment (4.1%), and metabolic syndrome (4%). The cumulative incidence and severity of late effects showed a consistent decline by the decade of diagnosis. Twenty-two percent of survivors are lost to follow-up. CONCLUSION: Survivors of childhood cancer treated on contemporary treatment protocols have a significantly lower side-effect profile. Attrition to long-term follow-up and psychosocial issues are significant concerns. Understanding the unique spectrum of late effects and establishing a holistic support system go a long way in ensuring the long-term physical and mental health and psychosocial concerns of childhood cancer survivors in low- and middle-income countries.

Caregiver burden in older Indian patients with cancer- Experience from a tertiary care center.

INTRODUCTION: Most of the long-term care for older adults with chronic or debilitating illnesses is provided by unpaid family members or informal caregivers. There is limited information on caregiver burden among caregivers of older patients with cancer in India. Hence, we assessed the prevalence and severity of caregiver burden among caregivers of older Indian patients with cancer. MATERIALS AND METHODS: This was an observational study conducted at the geriatric oncology clinic at Tata Memorial Centre, Mumbai, India. Caregivers of patients aged 60 years and over with a diagnosis of cancer were assessed for caregiver burden using the Zarit Burden Interview. Descriptive statistics were used for demographic and clinical variables. Factors impacting caregiver burden were analyzed using multiple linear regression analysis. RESULTS: Caregiver burden was assessed among 127 caregivers of older Indian patients with cancer. The median patient age was 69 years (range 60-90). Most patients were men (75.6%). There were 33 female caregivers (26%), and 94 male caregivers (74%). The median caregiver burden score was 12 (IQR 6-20). Caregiver burden was "little/none" in 97 (76.4%), "mild-moderate" in 25 (19.7%), "moderate-severe" in four (3.1%) and "severe" in one (0.8%) of the caregivers assessed. On multivariate analysis, factors that significantly impacted caregiver burden scores were the presence of psychological issues in the patient and the caregiver's educational level. DISCUSSION: Caregiver burden was low among caregivers of older Indian patients with cancer seen at a single center. Caregivers of patients with psychological disorders, and those who had less schooling reported higher caregiver burden.

Outcomes of Ewing sarcoma in adults over 40 years of age from a low-middle income country.

Introduction: The data on outcomes and toxicity in adult Ewing sarcoma (ES) patients, particularly those aged ≥40 years, is exceedingly scarce around the world, particularly in low- and middle-income countries (LMICs) and mandates research. Methods: The study involved histologically ascertained ES patients aged ≥40 years who registered at our institute from 2013 to 2018. Prospectively collected data were analysed for overall survival (OS), event-free survival (EFS) and chemotherapy-related toxicities. Results: There were 66 patients, of which 34 were non-metastatic, and 32 were denovo metastatic, recurrent or had doubtful metastasis. At presentation, median age was 46 years, and 42 (63.6%) had extra-skeletal primary and 24 (36.3%) had extremity tumours. Curative treatment was offered to 40 (60.6%) patients. Significant grade 3/4 toxicities in non-metastatic and metastatic cohort, respectively, were febrile neutropenia (61.3%, 37.5%), anaemia (58.1%, 37.5%), thrombocytopenia (45.2%, 25.0%), peripheral neuropathy (25.8%, 12.5%) and dyselectrolytemia (25.8%, 6.25%). Chemotherapy-related toxicity led to death in three patients in the metastatic cohort, versus none in the non-metastatic patients. The 5 year EFS and OS for non-metastatic cohort were 53.8% and 67.8%, while the same for metastatic cohort were 20.7% and 27.5%, respectively. On multivariate analysis, Eastern Cooperative Oncology Group-performance status >2 and metastasis at presentation predicted poorer EFS and OS. Additionally, raised lactate dehydrogenase, larger tumours (>8 cm) and palliative intent treatment predicted worse EFS, while extra-skeletal primary and female gender were indicators of worse OS. Conclusions: Older adult ES patients benefit from aggressive multimodality treatment even in LMIC infrastructure. However, careful patient selection, close monitoring and pertinent dose modifications is imperative due to higher propensity for potential toxicities.

Impact of a pediatric oncology nutrition program: Lessons learnt over a decade.

BACKGROUND: The management of malnutrition in children with cancer remains a challenge in low-middle-income countries (LMICs). We describe our pediatric oncology nutrition program and its impact over the past decade. METHODS: We evaluated the impact of our nutrition program in accordance with the International Society of Paediatric Oncology-Paediatric Oncology in Developing Countries (SIOP PODC) Nutritional Program Evaluation in the areas of service delivery (number served, increments in delivery, number of trained care providers), patients at-risk (proportion identified with malnutrition at diagnosis/follow-up), and efficiency of nutritional interventions (proportion assessed, proportion achieved healthy weight, clinicians trained). We analyzed available data for trends between 2009 and 2020, and comparisons were made using the Fisher t test. This study was approved by our institutional ethics committee. RESULTS: From 2010 to 2020, 17 749 children treated at our center were beneficiaries of the nutritional program, including assessment and intervention. During this period, trained pediatric nutritionists increased from 2 to 8; SIOP PODC level from 2 to 3-4, and nutrition budget increased 15-fold. At diagnosis (n = 5618) and six-month follow-up (n = 2674), 59.6% and 51.2% children were undernourished, 34.8% and 43% well nourished, and 4.7% and 5.7% overnourished. From 2016 onward, fewer children were undernourished at follow-up-69.5% (2016), 60% (2018), 54% (2019), and 55% (2020, P < 0.001). The program helped train over 500 clinicians in nutrition. CONCLUSIONS: Improved financial support and capacity building have helped build and sustain an effective nutrition program. Priority areas include implementation of best practices, early nutritional intervention, continued education, and locally relevant research.

Phase I Study Evaluating Dose De-escalation of Sorafenib with Metformin and Atorvastatin in Hepatocellular Carcinoma (SMASH).

BACKGROUND: This phase I dose de-escalation study aimed to assess the tolerability, safety, pharmacokinetics (PK), and efficacy of sequentially decreasing doses of sorafenib in combination (SAM) with atorvastatin (A, 10 mg) and metformin (M, 500 mg BD) in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients were enrolled in 1 of 4 sequential cohorts (10 patients each) of sorafenib doses (800 mg, 600 mg. 400 mg, and 200 mg) with A and M. Progression from one level to the next was based on prespecified minimum disease stabilization (at least 4/10) and upper limits of specific grade 3-5 treatment-related adverse events (TRAE). RESULTS: The study was able to progress through all 4 dosing levels of sorafenib by the accrual of 40 patients. Thirty-eight (95%) patients had either main portal vein thrombosis or/and extra-hepatic disease. The most common grade 3-5 TRAEs were hand-foot-syndrome (grade 2 and grade 3) in 3 (8%) and transaminitis in 2 (5%) patients, respectively. The plasma concentrations of sorafenib peaked at 600 mg dose, and the concentration threshold of 2400 ng/mL was associated with higher odds of achieving time to exposure (TTE) concentrations >75% centile (odds ratio [OR] = 10.0 [1.67-44.93]; P = .01). The median overall survival for patients without early hepatic decompensation (n = 31) was 8.9 months (95% confidence interval [CI]: 3.2-14.5 months). CONCLUSION: The SAM combination in HCC patients with predominantly unfavorable baseline disease characteristics showed a marked reduction in sorafenib-related side effects. Studies using sorafenib 600 mg per day in this combination along with sorafenib drug level monitoring can be evaluated in further trials.(Trial ID: CTRI/2018/07/014865).

Clinical outcomes and prognostic factors in children with B-cell lymphoblastic lymphoma (LBL) treated according to on modified BFM-90 protocol: Experience from a Tertiary cancer care center in India.

Pediatric B-cell lymphoblastic lymphoma (LBL) is a rare entity, and appropriate treatment for pediatric B-cell LBL is not well defined. While intensive ALL type regimens achieve long term survival of 90% across Western co-operative group trials, published data from Asian studies on long term outcomes are scarce. We retrospectively analyzed the data of pediatric B-cell LBL patients treated between January 2010 and December 2017 on a uniform protocol (modified BFM 90). Kaplan-Meier method was used to estimate the survival and Cox regression models to identify prognostic factors. Of 21 patients who received treatment on the modified BFM-90 protocol, 17(81%) were alive in remission, 3(14%) had relapse, and 1(4%) had treatment-related mortality (TRM) while in remission. Two of 3 relapsed patients subsequently expired. With a median follow-up of 66 months (range 6-114), 5-year event free survival (EFS) and overall survival (OS) were 80% (95% CI:71-89%) and 91% (95% CI:85-97%), respectively. While delayed presentation from symptom onset (p=0.030), and partial response at early (D35) interim assessment (p=0.025) had inferior EFS, patients with elevated baseline LDH had a worse OS (p=0.037). Outcomes of pediatric B-cell LBL patients treated on a modified BFM-90 protocol at a single center in India were excellent. In our study, higher disease burden manifested by elevated baseline LDH and delayed presentation (≥3months) and partial interim response portend poorer survival.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.2005725.

Survival outcomes with 12 weeks of adjuvant or neoadjuvant trastuzumab in breast cancer.

Background: There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment. Methods: This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity. Results: A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6-90 months), the median age was 46 (24-65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56-75%) and the OS was 76% (95% CI 67-85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients. Conclusion: The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer.

Resource-appropriate selection of osteosarcoma treatment protocols in low- and middle-income countries.

Osteosarcoma is a rare malignancy; however, it is still the most common primary bone tumor in adolescents and young adults. Chemotherapy improves survival indubitably in osteosarcoma; nevertheless, the concern is the stagnant progress since the last several decades. There are a handful of active agents and unresolved issues, especially in choosing the ideal chemotherapy regimen. The oncology community is in equipoise regarding the position of high-dose methotrexate (HDMTX), mandatory or adjunct. The choice of therapy becomes widely relevant, including in low- and middle-income countries (LMIC), where HDMTX administration brings additional complexities. Research into novel non-HDMTX-based protocols adapted to the available resources is pivotal in improving disease outcomes, especially in LMIC. The current review focuses on real-world challenges in decision-making and provides a comprehensive overview of the evolution of treatment protocols in LMIC.

Adolescent-adult nonmetastatic Ewing sarcoma-Experience from a large developing country.

BACKGROUND: Outcome and toxicity data in adolescent-adult Ewing sarcoma (AA-ES) patients are sparse and merits exploration. METHODS: Histopathologically confirmed, nonmetastatic AA-ES patients, who received standard institutional combination chemotherapy regimen (Ewing's family of tumors-2001 [EFT-2001]) comprising of ifosfamide plus etoposide and vincristine, doxorubicin plus cyclophosphamide, lasting a total of 12 months between 2013 and 2018, were analyzed for treatment-related toxicities, event-free survival (EFS), and overall survival (OS). RESULTS: There were 235 patients (primary safety cohort [PSC]) with median age of 23 (15-61) years; 159 (67.7%) were males, 155 (65.9%) had skeletal primary and 114 (48.5%) had extremity tumors. One hundred ninety-six (83.4%) were treatment naïve (primary efficacy cohort [PEC]) and of these 119 (60.7%) had surgery. In PEC, at a median follow-up of 36.4 (interquartile range [IQR] 20-55) months, estimated 3-year EFS and OS were 67.3% (95% CI 60.3-75.1%) and 91.1% (95% CI 86.7-95.7%), respectively. Of these, 158 (80.6%) complying with intended treatment, at a median follow-up of 39 (IQR 26-57) months had an estimated 3-year EFS of 68.2% (95% CI 60.3-76.1%). In multivariable analysis, good prognostic factors included longer symptom(s) duration (HR 0.93, 95% CI 0.86-0.994), ≥99% necrosis (HR 0.30, 95% CI 0.11-0.77), and treatment completion (HR 0.32, 95% CI 0.14-0.74). Among PSC, grade 3-4 toxicities were febrile neutropenia (119, 50.6%), anemia (130, 55.3%), peripheral neuropathy (37, 15.7%), with three (1.3%) chemo-toxic deaths. CONCLUSIONS: The outcomes of AA nonmetastatic ES patients treated with EFT-2001 regimen were comparable to those reported by others, with acceptable toxicity. This regimen can be considered a standard of care in AA-ES.

Robust Antitumor Activity and Low Cytokine Production by Novel Humanized Anti-CD19 CAR T Cells.

Recent studies have described the remarkable clinical outcome of anti-CD19 chimeric antigen receptor (CAR) T cells in treating B-cell malignancies. However, over 50% of patients develop life-threatening toxicities associated with cytokine release syndrome which may limit its utilization in low-resource settings. To mitigate the toxicity, we designed a novel humanized anti-CD19 CAR T cells by humanizing the framework region of single-chain variable fragment (scFv) derived from a murine FMC63 mAb and combining it with CD8α transmembrane domain, 4-1BB costimulatory domain, and CD3ζ signaling domain (h1CAR19-8BBζ). Docking studies followed by molecular dynamics simulation revealed that the humanized anti-CD19 scFv (h1CAR19) establishes higher binding affinity and has a flexible molecular structure with CD19 antigen compared with murine scFv (mCAR19). Ex vivo studies with CAR T cells generated from healthy donors and patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) expressing either h1CAR19 or mCAR19 showed comparable antitumor activity and proliferation. More importantly, h1CAR19-8BBζ T cells produced lower levels of cytokines (IFNγ, TNFα) upon antigen encounter and reduced the induction of IL6 cytokine from monocytes than mCAR19-8BBζ T cells. There was a comparable proliferation of h1CAR19-8BBζ T cells and mCAR19-8BBζ T cells upon repeated antigen encounter. Finally, h1CAR19-8BBζ T cells efficiently eliminated NALM6 tumor cells in a preclinical model. In conclusion, the distinct structural modification in CAR design confers the novel humanized anti-CD19 CAR with a favorable balance of efficacy to toxicity providing a rationale to test this construct in a phase I trial.

Efficacy and safety of neoadjuvant chemotherapy (NACT) with paclitaxel plus carboplatin and oral metronomic chemotherapy (OMCT) in patients with technically unresectable oral squamous cell carcinoma (OSCC).

A combination of maximum tolerated dose and metronomic chemotherapy schedule may lead to synergistic effects with acceptable toxicity. We assessed the efficacy and safety of this combination as neoadjuvant chemotherapy (NACT) in 14 patients with technically unresectable oral squamous cell carcinoma. They received NACT with paclitaxel-carboplatin and triple oral metronomic chemotherapy (OMCT) (methotrexate, celecoxib and erlotinib). Patients were assessed clinically and radiologically after a minimum of two cycles for resectability. Primary tumour site was buccal mucosa and oral tongue in 12 (86%) and 2 (14%) patients, respectively. The median number of NACT administered was three. The tumours of nine (65%) patients showed partial response and none of the patients had tumour progression. The tumours of nine patients (65%) were deemed resectable after NACT. Median progression free survival was 11.4 months (95% CI = 7.9-15 months) and median overall survival (OS) was not reached. OS at 15 months was 63.5% (95% CI = 37.8%-89.2%). Grade 3 or 4 haematological toxicities were seen in eight (57%) patients. Paclitaxel-carboplatin combined with OMCT is a well-tolerated and less resource intensive NACT regimen which leads to favourable resection rate and survival.

Favorable outcomes and reduced toxicity with a novel vinblastine-based non-high dose methotrexate (HDMTX) regimen (modified MCP-842) in pediatric anaplastic large cell lymphoma (ALCL): experience from India.

Anaplastic large cell lymphoma (ALCL) is a rare form of non-Hodgkin lymphoma (NHL) in children. Most treatment regimens include high-dose methotrexate (HDMTX), which is logistically difficult to administer in resource-limited settings. We evaluated the outcomes of pediatric ALCL patients treated on a uniform protocol (Modified Multicentric Protocol, MCP-842 regimen) at our hospital between January 2005 and December 2016. Of the 68 patients who received treatment on the Modified MCP842 protocol, 46 patients are alive in remission, 11(16%) had disease progression, 9(13%) relapsed after achieving remission, and 5(7%) had treatment-related mortality (TRM). Seventeen of 20 relapsed/progressed patients subsequently expired. With a median follow-up of 55 months (range 2-165 months), the 4-year event-free survival (EFS) and overall survival (OS) are 63% (95% CI of 50-73%) and 70%(95% CI of 57-79%), respectively. An indigenous protocol using vinblastine (without HDMTX and steroids) is feasible in a resource-limited setting and achieves outcomes comparable to regimens incorporating HDMTX, with lower toxicity.

A Novel Case of ABL2 Chromosomal Rearrangement in High-Risk B-Cell Acute Lymphoblastic Leukemia.

OBJECTIVES: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) accounts for ~15% of patients with high-risk ALL with an activated tyrosine kinase profile similar to Philadelphia chromosome positive ALL, without the presence of BCR-ABL1 rearrangement. ABL-class genes (ABL1, ABL2, PDGFRB, CSF1R and CRLF2) comprise the second major subgroup of Ph-like ALL cases but presence of ABL2 gene rearrangement in leukemia is rarely reported. We report a novel case of ABL2 chromosomal rearrangement that results from t(1;7)(q25;q32) in a patient with high-risk ALL.

Bisphosphonate Combination Therapy in the Management of Postchemotherapy Avascular Necrosis of the Femoral Head in Adolescents and Young Adults: A Retrospective Study From India.

PURPOSE: With improved survival after chemotherapy for acute lymphoblastic leukemia (ALL), it is imperative to maintain good quality of life as part of the management of post-therapy adverse effects. Avascular necrosis of the femoral head (AVNFH) is one such adverse effect. A need exists for a therapy that ameliorates discomfort, provides a productive life, is cost effective, and is joint preservative. We conducted the current study to evaluate the response to bisphosphonate in the nonsurgical management of AVNFH in adolescents and young adults (AYA) who receive treatment for ALL. MATERIALS AND METHODS: This is a retrospective study of 20 AYA patients-34 affected hips-who received zolendronic acid 5 mg intravenously each year along with oral alendronate 70 mg weekly for 3 years. Clinical evaluation was performed by using the Visual Analog Scale and the Harris Hip Score. Radiographs were used to classify the Ficat-Arlet stage, monitor radiologic collapse, and evaluate the rate of progression. RESULTS: Pain relief with a drop in the Visual Analog Scale score was observed at a mean duration of 5.2 weeks (range, 3 weeks to 11 weeks) after the start of therapy. Radiologic progression by one grade was observed in 12 hips (35.3%), and only one hip (2.94%) showed progression by two grades. At a mean follow-up of 50.3 months, 31 affected hips (91.1%) had a satisfactory clinical outcome and had not required any surgical intervention. The proportion of hips that required total hip arthroplasty were 0%, 5%, and 22.2% in Ficat-Arlet stage I, II, and III, respectively. CONCLUSION: The combination of intravenous zolendronic acid and oral alendronate provides a pragmatic solution for the management of AVNFH after therapy for ALL in AYA patients. This therapy is safe, effective, and well tolerated.

Phase III randomized trial comparing intravenous to oral iron in patients with cancer-related iron deficiency anemia not on erythropoiesis stimulating agents.

AIM: We aimed to find the optimal route of iron supplementation in patients with malignancy and iron deficiency (true or functional) anemia not receiving erythropoiesis stimulating agents (ESA). METHODS: Adult patients with malignancy requiring chemotherapy, hemoglobin (Hb) <12 g/dL and serum ferritin <100 mcg/mL, transferrin saturation <20% or hypochromic red blood cells >10% were randomized to intravenous (IV) iron sucrose or oral ferrous sulfate. The primary endpoint was change in Hb from baseline to 6 weeks. Secondary endpoints included blood transfusion, quality of life (QoL), toxicity, response and overall survival. RESULTS: A total of 192 patients were enrolled over 5 years: 98 on IV arm and 94 on oral arm. Median age was 51 years; over 95% patients had solid tumors. The mean absolute increase in Hb at 6 weeks was 0.11 g/dL (standard deviation [SD]: 1.48) in IV arm and -0.16 g/dL (SD: 1.36) in oral arm, P = 0.23. Twenty-three percent patients on IV iron and 18% patients on oral iron had a rise in Hb of ≥1 g/dL at 6 weeks, P = 0.45. Thirteen patients (13.3%) on the IV iron arm and 14 patients (14.9%) on the oral arm required blood transfusion, P = 1.0. Gastrointestinal toxicity (any grade) developed in 41% patients on IV iron and 44% patients on oral iron, P = 1.0. 5 patients on IV iron and none on oral iron had hypersensitivity, P = 0.06. QoL was not significantly different between the two arms. CONCLUSION: IV iron was not superior to oral iron in patients with malignancy on chemotherapy and iron deficiency anemia.

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.

Chicken pox infection in patients undergoing chemotherapy: A retrospective analysis from a tertiary care center in India.

There is paucity of data on the incidence, severity and management of chicken pox in patients receiving active chemotherapy for cancer. From October 2010 to October 2011, patients were included in this study if they developed a chicken pox infection during their chemotherapy. The details of patients' cancer diagnosis and treatment along with clinical and epidemiological data of the chicken pox infections were assessed from a prospectively maintained database. Twenty-four patients had a chicken pox infection while receiving chemotherapy and/or radiotherapy. The median age of the patients was 21 years, and two-thirds of the patients had solid tumor malignancies. Overall, eight (33%) patients had complications, six (25%) patients had febrile neutropenia, four (17%) had diarrhea/mucositis, and four (17%) had pneumonia. The median time for recovery of the infection and complications in the patients was 9.5 days (5-29 days), whereas for neutropenic patients, it was 6.5 days (3-14 days). The median time for recovery from chicken pox infections in neutropenic patients was 10 days (5-21 days), compared with 8.5 days (0-29 days) in non-neutropenic patients (P=0.84). The median time for recovery from infections was 8.5 days in patients with comorbidities (N=4), which was the same for patients with no comorbidities. The clinical presentation and complication rates of chicken pox in cancer patients, who were on active chemotherapy, are similar to the normal population. The recovery from a varicella infection and complications may be delayed in patients with neutropenia. The varicella infection causes a therapy delay in 70% of patients. Aggressive antiviral therapy, supportive care and isolation of the index cases remain the backbone of treatment.