Efficacy and Safety of Oral Metronomic Chemotherapy in Recurrent Refractory Advanced Gynaecological Cancer: An Experience From the Regional Cancer Centre of Eastern India.

INTRODUCTION: The outcome of recurrent/metastatic gynaecological malignancy has drastically improved with the introduction of poly(ADP-ribose) polymerase inhibitors and immunotherapy, but the use of these drugs in routine practice is complicated due to access barriers and their high cost in developing countries. The purpose of this study is to present the clinical response, outcome and safety of oral metronomic chemotherapy (OMCT) in resource-limited, financially constrained populations. METHODS: This is a retrospective study on patients with advanced gynaecological cancer treated at Chittaranjan National Cancer Institute, Kolkata, India, from 2021 to 2023. The patients were treated with one of these two regimens: a split-dose course of cyclophosphamide (50 mg orally once daily for 21 days) and capecitabine (500 mg twice daily continuous) or a fixed-dose combination (capecitabine 1800 mg and cyclophosphamide 80 mg orally for 14 days in every 21 days) until disease progression or unacceptable toxicities occurred. All data was captured from the hospital's medical records until June 2023. Toxicity data was reported per the Common Terminology Criteria for Adverse Events (CTCAE) v5.1, and progression-free survival (PFS) was estimated using Kaplan-Meier methods. RESULTS: Among 34 screened patients, 10 were excluded due to noncompliance. This study analysed 24 patients with a median age at diagnosis of 56 years (IQ range 44-75). Sixteen (67%) patients were at stage IV disease with an Eastern Cooperative Oncology Group (ECOG) performance status of 3. Ovarian and cervical cancers were 80% and 20%, respectively; among them, 16 (67%) patients were platinum-refractory. Forty-two per cent of patients received three lines of chemotherapy before OMCT. A split course versus fixed dose was given to 67% versus 33% of the population; the best responses per the Response Evaluation Criteria in Solid Tumours v1.1 were complete response in 12%, partial response in 67% and stable disease in 21%. The most common toxicities were grade I anaemia (54%), grade I chemotherapy-induced nausea and vomiting (46%), grade I fatigue (42%) and grade I neutropenia (21%). Twenty-five per cent of patients were offered next-line systemic therapy after progression. The entire cohort had a median PFS of nine months (95%, CI: 5.2-12.7). Cox regression analysis identified a median PFS of 12 months (95%, CI: 6.2-17.7) among platinum-refractory groups. CONCLUSION: OMCT was a well-tolerated, affordable regimen with durable clinical response and survival outcome (median PFS of nine months) in recurrent, refractory advanced gynaecological cancer and can be offered to patients at resource-limited centres.

Hippocampal avoidance whole brain radiotherapy in brain metastasis using volumetric modulated arc therapy: experience from a Regional Cancer Centre of Eastern India.

Background: Whole-brain radiotherapy is associated with neurocognitive decline and decreased quality-of-life (QOL) among survivors of brain metastasis. Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) has shown advantage in delaying or preventing the neurocognitive decline while maintaining disease control. This study was done to assess the benefits and feasibility of HA-WBRT in patients with cerebral metastasis in terms of preservation of neurocognitive function and quality of life. Materials and methods: 27 patients with brain metastasis treated by HA-WBRT and having the records of detailed neurocognitive-assessments were analysed from the database of our hospital. The patients were treated with HA-WBRT to a total dose of 30 Gy in 10 fractions with LINAC based IMRT using the VMAT technique. Cognitive function assessment was carried out using "Examination of the Cognitive Functions" scale provided by Bangur-Institute-of-Neurosciences, Kolkata, 2 weeks prior to radiotherapy and post-treatment two-monthly up to 6 months followed by every 3 months till the last follow up. QOL was assessed at the same interval using the Functional Assessment of Cancer Therapy with Brain Subscale (FACT-BR). Follow-up was done till the date of death. Results: Mean relative cognitive decline percentage decreased over subsequent follow-up visits and was 13% (SD ± 6%), 5% (SD ± 5%), 5% (SD ± 9%) and 2% (SD ± 12%) at 2 months, 6 months, 9 months and 12 months, respectively (p ≤ 0.05). Statistically significant improvement was seen in the mean social-wellbeing (SWB) parameter of QOL (8%. ± 13%, 12%. ± 16%, 7%. ± 20%, no change at 2 months, 4 months, 6 months and 9 months, respectively) (p ≤ 0.05). Mean relative decline in the Emotional-Well Being (EWB) parameter was significant only at 12 months and was 20% (SD ± 35%) (p = 0.04). Mean FACT-BR total Score showed a slight decrease till 9 months from baseline, and then showed a slight improvement up to 12 months. Conclusion: HA-WBRT is feasible with LINAC-based IMRT using the VMAT technique and beneficial to the patients in preserving neurocognitive function and quality of life without compromising disease control.

Immunomodulated anterior chemotherapy followed by concurrent chemoradiotherapy in locally advanced tongue cancer: An Institutional experience.

CONTEXT: Sequential induction chemotherapy with cisplatin and 5-fluorouracil (PF) along with interferon-alpha2b and concurrent chemoradiation offers superior loco-regional control for locally advanced carcinoma of oral tongue. AIMS: The study was designed to evaluate the beneficial role of induction PF chemotherapy and interferon-alpha2b followed by chemoradiation over definitive chemoradiation only for patients with locally advanced carcinoma of oral tongue. SETTINGS AND DESIGN: Phase II randomized, prospective, open-labeled, single-institutional study. METHODS AND MATERIAL: Fifty patients were randomized into 2 arms. Arm A patients were treated with induction chemotherapy with PF regimen for 3 cycles and interferon alpha 2b, 3MU biweekly for 6 such followed by chemoradiation with cisplatin 30 mg/ m(2)/ week and external radiotherapy. Arm B patients received chemoradiation only, in the same dose schedule as in Arm A. STATISTICAL ANALYSIS USED: Chi-square test was done to find out the statistical correlation between the two arms. For plotting the disease-free survival (DFS) and overall survival (OS) for the two arms, Kaplan-Meier method was used. RESULTS: The loco-regional response rate of patients treated with interferon containing induction chemotherapy followed by concurrent chemoradiation was superior to concurrent chemoradiation only. However the toxicities and treatment interruption were more in patients treated with induction chemotherapy. CONCLUSIONS: In locally advanced carcinoma of oral tongue, induction chemotherapy with cisplatin and 5-fluorouracil (PF) along with interferon alpha 2b followed by concurrent chemoradiation may produce superior loco-regional control with manageable toxicities that needs to be validated by more randomized trials with adequate number of patients.

Recurrent Glioblastoma: Where we stand.

Current first-line treatment regimens combine surgical resection and chemoradiation for Glioblastoma that provides a slight increase in overall survival. Age on its own should not be used as an exclusion criterion of glioblastoma multiforme (GBM) treatment, but performance should be factored heavily into the decision-making process for treatment planning. Despite aggressive initial treatment, most patients develop recurrent diseases which can be treated with re-resection, systemic treatment with targeted agents or cytotoxic chemotherapy, reirradiation, or radiosurgery. Research into novel therapies is investigating alternative temozolomide regimens, convection-enhanced delivery, immunotherapy, gene therapy, antiangiogenic agents, poly ADP ribose polymerase inhibitors, or cancer stem cell signaling pathways. Given the aggressive and resilient nature of GBM, continued efforts to better understand GBM pathophysiology are required to discover novel targets for future therapy.

Tumor bed boost in breast cancer: Brachytherapy versus electron beam.

BACKGROUND: The prospective study aimed to evaluate the effectiveness of Electron beam or HDR 192Ir Interstitial Implant used as a boost in breast Conservation cases after completion of EBRT. The two therapeutic modalities were compared in terms of the following parameters; i.e. cosmesis, optimization of tumor bed boost, local control, toxicity, and DFS. MATERIALS AND METHODS: The EBRT dose used was 50 Gy in 25 fractions over 5 weeks time. Target delineation of boost treatment was done by CT scan or by high resolution USG. EBRT will be immediately followed by local boost at the primary tumor bearing site of breast with 8 to12 MeV electron beam to a dose of 15 Gy in 6 fractions (Arm A) or with HDR 192Ir interstitial brachytherapy to a dose of 15 Gy in 3 fractions at 6 hours apart (Arm B). RESULTS: The excellent cosmesis achieved with electron beam therapy in Arm A was found to be statistically significant (P = 0.025). Local relapse was absent in both the arms. One distant metastasis occurred in Arm A within 10 months of initiation of treatment and one distant metastasis in Arm B came out within 3 months of starting of therapy. CONCLUSION: The study has shown good cosmetic result with electron boost and 100% local control with both the technique. However if there is a more number of patients with longer period of follow up we could have got the actual picture to verify our results and assess long term survival data.

Addition of gemcitabine to standard therapy in locally advanced cervical cancer: A randomized comparative study.

BACKGROUND: The concurrent chemoradiotherapy for cervical cancer treatment is well accepted since 1999. This randomized, phase III trial aimed to observe if any improved outcome could be obtained capitalizing on the synergistic activity of gemcitabine, cisplatin, XRT. MATERIALS AND METHODS: Stage IIB-IIIB, 18-70 years of age, KPS score ≥70, were randomized to control group and study group. Control group received cisplatin 40 mg/m(2) weekly with concurrent XRT, followed by brachytherapy and study group received gemcitabine 125 mg/m(2) weekly top of the same control group treatment. The primary end point was pathological response and toxicities along with patient compliance to treatment, late reactions, DFS and OS. Fifty patients were randomized between two arms. RESULTS: The complete response in study and control arm was 96% and 88% respectively. Toxicities was significantly high in the study group compared to control group [leucopenia (P=0.015), skin reaction (P=0.03) and bleeding (P=0.019)]. Local recurrence rate: 8% in study arm, none in control arm. The distant failure prevailed in control arm (20% vs. 8%). On a median follow up of 21 months in control arm, the DFS was 73% whereas 83% in study arm in 16 months (P=0.69). OS in the study arm was 100% and 84.5% in the control arm (P=0.14). CONCLUSIONS: If the toxicity can be managed adequately in the combination chemo radiation group, it may produce an improvement in response. Survival benefit can also be obtained by introducing gemcitabine to cisplatin as radio sensitizer.

Bilateral angiosarcoma of breast in a young lady.

We report a young lady with bilateral angiosarcoma of breast because of its rarity. A 29 year old unmarried female presented with bilateral breast lump. She underwent bilateral mastectomy with axillary dissection histopathology of which showed low grade angiosarcoma of left breast and high grade angiosarcoma of right breast. CT Thorax revealed right hilar and right mediastenal lymph nodes. She was treated with radiotherapy and chemotherapy postoperatively.