A Retrospective Cohort Study to Evaluate the Outcomes of HIV-Associated High-Grade B-Cell Non-Hodgkin Lymphoma (NHL) Treated with Dose Adjusted EPOCH (+/-R) Regimen.

High-grade B-cell NHL's are more common in seropositive patients. They are biologically different from their seronegative counterparts. We report our analysis on our cohort of patients who were treated with DA-EPOCH(+/-R). We retrospectively analyzed treatment-naïve HIV-associated High-grade B-cell NHL patients (aged ≥ 18) treated with DA-EPOCH(+/-R) regimen from 2011 to 2015. Descriptive statistics were summarized with median and range; survival outcomes were analyzed with Kaplan-Meier method. The cohort comprised of 40 patients [DLBCL(19), Burkitt's Lymphoma(16), High-grade B-Cell Lymphoma-Unclassifiable(09), and Plasmablastic Lymphoma(01)] and the median CD4 + T cell count was 202/mm3. CNS prophylaxis was administered with intrathecal methotrexate to 90% of patients. With a median follow-up of 72 months, an estimated 5-year OS was 82.5%, and 5-PFS was 77.5%. There were 9 deaths, and 9 patients had progression. At least 4 cycles of chemotherapy were administered to 35 (93%) patients, with 28 (70%) receiving 6 cycles. Grade 3-4 toxicities were seen in 33 (83%) patients- febrile neutropenia (65%) being the most common followed by mucositis (25%) and peripheral neuropathy (13%). There was no difference in survival based on IPI, CD 4 + T cell count, CDI, or duration of HIV. DA-EPOCH(+/-R) is a highly effective regimen in seropositive high-grade B-cell lymphoma, even in the presence of adverse features. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01652-3.

Cardiac function in pediatric Ewing sarcoma during and after treatment: A longitudinal study.

BACKGROUND: While anthracycline therapy has been shown to improve outcomes in Ewing sarcoma, it may be associated with severe and even fatal cardiac dysfunction. We evaluated the burden and determinants of cardiac dysfunction in pediatric Ewing sarcoma (pES). METHODS: This retrospective study included children aged 0-18 years with pES treated at our center with the EFT 2001 protocol (anthracycline and cyclophosphamide containing regimen), with/without radiation therapy from January 2001 to December 2018. Cardiac dysfunction was defined as left ventricular (LV) ejection fraction with an absolute value <50%. RESULTS: Amongst 650 eligible patients (median age at diagnosis 12 years and median follow-up duration 69 months), 85 (13%) developed cardiac dysfunction, at a median 13 months (range: 1-168 months). The cumulative incidence of cardiac dysfunction was 5.7% at 12 months, 12% at 2 years, 13% at 3 years, 14% at 5 years, and 15 % at 10 years. At a median follow-up duration of 25 (range: 3-212) months, 21 (24.7%) patients had normalization of LV function, whereas nine (10.6%) patients died of cardiac causes. Older age at diagnosis (7-12 years OR 5.1, p = .01, 13-18 years, OR 3.9, p = .03), female sex (OR 2.3, p = .004), undernutrition (OR 2.9, p = .001), and chest wall location (OR 8.7, p = .08) were risk factors for cardiac dysfunction. CONCLUSIONS: Children with Ewing sarcoma have a high incidence of cardiac dysfunction, which continues to develop even years after therapy, underlining the need for life-long surveillance. Undernourished children are at a higher risk for cardiac dysfunction and need stringent monitoring.

Concurrent chemoradiation and brachytherapy alone or in combination with nelfinavir in locally advanced cervical cancer (NELCER): study protocol for a phase III trial.

INTRODUCTION: In locally advanced cervical cancer, nodal, local and distant relapse continue to be significant patterns of relapse. Therefore, strategies to improve the efficacy of chemoradiation are desirable such as biological pathway modifiers and immunomodulating agents. This trial will investigate the impact of nelfinavir, a protease inhibitor that targets the protein kinase B (AKT) pathway on disease-free survival (DFS). METHODS AND ANALYSIS: Radiosensitising effect of nelfinavir in locally advanced carcinoma of cervix is a single-centre, open-label, parallel-group, 1:1 randomised phase-III study. Patients aged over 18 years with a diagnosis of carcinoma cervix stage III are eligible for the study. After consenting, patients will undergo randomisation to chemoradiation and brachytherapy arm or nelfinavir with chemoradiation and brachytherapy arm. The primary aim of the study is to compare the difference in 3-year DFS between the two arms. Secondary aims are locoregional control, overall survival, toxicity and quality of life between the two arms. Pharmacokinetics of nelfinavir and its impact on tumour AKT, programmed cell death ligand 1, cluster of differentiation 4, cluster of differentiation 8 and natural killer 1.1 expression will be investigated. The overall sample size of 348 with 1 planned interim analysis achieves 80% power at a 0.05 significance level to detect a HR of 0.66 when the proportion surviving in the control arm is 0.65. The planned study duration is 8 years. ETHICS AND DISSEMINATION: The trial is approved by the Institutional Ethics Committee-I of Tata Memorial Hospital, Mumbai (reference number: IEC/0317/1543/001) and will be monitored by the data safety monitoring committee. The study results will be disseminated via peer-reviewed scientific journals, and conference presentations. Study participants will be accrued after obtaining written informed consent from them. The confidentiality and privacy of study participants will be maintained. TRIAL REGISTRATION NUMBER: The trial is registered with Clinical Trials Registry-India (CTRI/2017/08/009265) and ClinicalTrials.gov (NCT03256916).

Outcomes of Cervical Cancer in HIV-Positive Women Treated With Radiotherapy at a Tertiary Care Center in India.

PURPOSE: There are limited data on management of cervical cancer in women living with HIV in the modern antiretroviral therapy era. The study aimed to evaluate outcomes and toxicities of these patients treated with radiotherapy. MATERIALS AND METHODS: A retrospective analysis of HIV-positive cervical cancer patients treated with radiotherapy between 2011 and 2018 was conducted at a tertiary care center in India. RESULTS: Eighty-two HIV-positive cervical cancer patients treated with radiotherapy were identified. Their median age was 45 years. Seventy-four (90%) patients received radiotherapy with curative-intent and eight patients received palliative radiotherapy. Median CD4 count at the start of treatment was 342 cells/mm3 (interquartile range: 241-531). Among patients planned for definitive radiotherapy, concurrent cisplatin was planned in 52 (70%) patients with a median of four chemotherapy cycles, and 81% (n = 60) patients received brachytherapy. Among patients who received brachytherapy, the median prescription dose was 80 Gy. Seventy-seven patients completed their prescribed treatment. At a median follow-up of 37 months, 3-year disease-free survival of patients planned with curative-intent was 54%. On multivariate analysis, treatment completion was associated with favorable disease-free survival. Grade III/IV acute gastrointestinal toxicity was seen in five (6.8%) patients, whereas 30% patients had grade III/IV acute hematologic toxicity. All these patients completed their planned radiotherapy with good supportive care. CONCLUSION: Standard treatment of chemoradiation should be planned in women living with HIV with well-managed HIV presenting with locally advanced cervical cancer. Our study highlights the need for optimal management of these patients by a multidisciplinary team with intensive supportive care to ensure completion of planned treatment to achieve better outcomes.

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.

Cardiac morbidity & mortality in patients with breast cancer: A review.

Cardiovascular disease (CVD) and breast cancer cause substantial morbidity and mortality in women and are major public health concerns. Breast cancer survivors are at a greater risk for CVD-related mortality compared to women without breast cancer. Breast cancer and cardiovascular diseases share a number of common risk factors. Breast cancer treatments like anthracycline based chemotherapy, novel targeted therapy and radiation therapy can cause cardiotoxicity. With improvements in breast cancer prevention and treatment, there is a significant improvement in survival and this shifts focus from disease control to long term effects of treatment and quality of life. Assessing CVD and minimizing complications from cancer therapy are important treatment goals.

Asymptomatic myocardial metastasis from cancers of upper aero-digestive tract detected on FDG PET/CT: a series of 4 cases.

Metastatic involvement of the heart is a rare occurrence and remains undiagnosed until autopsy. In some instances, patients may have cardiac symptoms, leading to ante-mortem diagnosis. Although most primary cancers have been documented to metastasize to heart, the existing literature on cancers of upper aero-digestive tract is an exception, with only a few reports. We report four cases of upper aero-digestive tract cancers, three of which arise from oral cavity, one from lower esophagus, metastasising to the myocardium, detected on 18 F - Fluoro-deoxy-glucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) study , in the absence of related symptoms.

Malignancies in HIV: the Indian scenario.

PURPOSE OF REVIEW: India has the second largest number of HIV/AIDS patients in the world; however, studies done in the area of HIV-related malignancies are few. With the availability of highly active antiretroviral therapy and treatment and prevention of opportunistic infections, an increase in life expectancy of HIV-infected individuals and an increase in HIV-related malignancies is expected. The purpose of this review is to put forth the Indian scenario of HIV-related malignancies. RECENT FINDINGS: About 2.5 million Indians have HIV/AIDS. Non-Hodgkin's lymphoma and cervical cancer were found to occur in a higher proportion among the HIV-infected individuals in India as compared with non-HIV-infected individuals. The incidence of AIDS-related primary central nervous system lymphoma is low in India. Kaposi's sarcoma is rare in India. Amongst the non-AIDS defining cancers anal cancer, testicular cancer, Hodgkin's disease, colon cancer and certain head and neck cancer sites in men and vaginal cancers among women were found to occur more frequently. SUMMARY: With the availability of highly active antiretroviral therapy an increased mortality and morbidity due to neoplastic diseases is expected in the future. As India is a large country and geographically and culturally diverse, large-scale studies need to be done linking the regional cancer centres with the AIDS centres across the country to evaluate the exact burden of HIV-related malignancies.

Spectrum of HIV/AIDS related cancers in India.

OBJECTIVE: To study the cancer pattern among HIV positive cancer cases. METHOD: The study group included patients registered in the HIV Cancer clinic at the Tata Memorial Hospital (TMH), Mumbai, which is the largest tertiary referral cancer center in India. We used the gender and age-specific proportions of each cancer site of the year 2002 that was recorded in the Hospital Cancer Registry to estimate an expected number of various cancer sites among HIV positive cancer patients during the period 2001-2005. The observed number of site-specific cancer cases was divided by the expected number to obtain proportional incidence ratio (PIR). RESULTS: No case of Kaposi's sarcoma was observed. Increased proportion of non-Hodgkin's lymphoma (NHL) was observed (PIR in males = 17.1, 95%CI 13.33-21.84, females = 10.3, 95%CI 6.10-17.41). In males, PIR was increased for anal cancer (PIR = 10.3, 95%CI 4.30-24.83), Hodgkin's disease, testicular cancer, colon cancer, and few head and neck cancer sites. Among females, the PIRs for cervical cancer (PIR = 4.1, 95%CI 2.90-5.75), vaginal cancer (PIR = 7.7, 95%CI 2.48-23.85), and anal cancer (PIR = 6.5, 95%CI 0.91-45.88) were increased. CONCLUSIONS: The absence of Kaposi's sarcoma and increased PIRs for certain non-AIDS defining cancers among HIV infected cancer cases indicates a different spectrum of HIV associated malignancies in this region. The raised PIR for cervical cancer emphasizes the urgent need for screening programs for cervical cancer among HIV infected individuals in India.