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Approximately 20%-25% of patients with metastatic castration-resistant prostate cancer (mCRPC) harbor a deleterious germline or somatic mutation in the homologous recombination repair (HRR) pathway genes, which is involved in the repair of double-stranded DNA damage. Half of these mutations are germline, while the remaining are exclusively somatic. While polyadenosine 5'diphosphoribose [poly (ADP-ribose)] polymerase inhibitors, such as olaparib and rucaparib, are effective in this subgroup, their widespread use is limited due to the associated high cost, especially in resource-constrained settings. Notably, platinum agents like carboplatin have exquisite sensitivity to cells with defective DNA repair machinery. Carboplatin, a conventional, inexpensive chemotherapeutic agent, offers a potential alternative treatment in such patients. Several retrospective small case series support this hypothesis. However, there are no prospective clinical trials of carboplatin in patients with mCRPC with HRR mutations. The primary objective is to assess the objective response rate of 3 weekly carboplatin treatments in patients with mCRPC harboring deleterious mutations in the HRR pathway genes and previously treated with a taxane or a novel antiandrogen agent. The secondary objectives include progression-free survival, health-related quality of life, and safety profile of carboplatin. Patients diagnosed with mCRPC harboring HRR pathway mutations previously treated with docetaxel or novel antiandrogen agents (abiraterone, enzalutamide, apalutamide, or darolutamide) or both will be eligible. Genes involved directly or indirectly in the HRR pathway will be tested. In this single-arm phase II study, we will screen approximately 200 patients to enroll 49 patients, and carboplatin (dosing at the area under curve=5) will be administered every 3 weeks until progression or intolerable side effects. The primary end point will be assessed as the proportion of patients with a reduction of serum prostate-specific antigen by more than 50% from enrollment. Secondary outcomes include progression-free survival-soft-tissue disease progression (by response evaluation criteria in solid tumors, version 1.1, and bone lesion progression using Prostate Cancer Clinical Trials Working Group 3 criteria), health-related quality of life during carboplatin treatment using the Functional Assessment of Cancer Therapy-Prostate questionnaire and the European Organisation for Research and Treatment of Cancer questionnaire and safety profile of carboplatin (National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0). The trial started enrollment in September 2023. This trial is ongoing, and 12 patients have been recruited to date. All 49 participants will be enrolled according to plan. This prospective phase II trial represents a critical step toward addressing the therapeutic gap in patients with mCRPC harboring HRR pathway mutations, particularly in demographic regions with limited access to poly (ADP-ribose) polymerase inhibitors. Outcomes from this study will inform clinical practice and guide future phase III randomized trials, ultimately improving patient outcomes globally. Clinical Trials Registry of India CTRI/2023/04/051507; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=Njc0NjU=&Enc=&userName=. DERR1-10.2196/54086.

IntroductionDiffuse intrinsic pontine glioma (DIPG) is the most common form of brainstem glioma. The present study was performed to assess if hypofractionated radiotherapy completed in < 3 weeks with temozolomide improves survival in DIPG.Material and methodsThe present study is a phase II open label randomized trial. The study included newly diagnosed patients with DIPG. Patients in arm A received conventional fractionated RT of 60 Gy in 30 fractions over 6 weeks while patients in arm B received hypo-fractionated radiotherapy of 39 Gy in 13 fractions over 2.6 weeks along with concurrent Temozolomide (TMZ) 75 mg/m2 from day 1 to day 17 followed by adjuvant TMZ for six cycles. The survival analysis was performed with modified intention to treat analysis.ResultsA total of 35 patients were randomized. 33 patients were evaluable. 93% (n = 14) of patients in the conventional arm completed treatment while only 17% (n = 3) of the children could complete planned course of treatment in the experimental arm. The median overall survival (OS) was 11 months (95% CI − 7.5 to 14.5 months) in the conventional arm and 12 months (95% CI − 10.5 to 13.5 months) in the experimental arm (p = 0.208). 28% (n = 5) patients in the experimental arm developed grade 3 or 4 hematological toxicity.ConclusionThe above study shows that hypofractionated radiotherapy with concurrent and adjuvant temozolomide does not improve OS and has higher hematological toxicity. Conventional radiotherapy remains the standard of care.

Pineal region tumors are rare and a heterogenous group of primary central nervous system tumors which are primarily classified as germ cell tumors and non-germ cell tumors. Chemotherapy and radiotherapy as the primary treatment modalities have been reported to result in good outcomes. We discuss the case of a young girl who presented to our emergency department in an unconscious state and had a large lesion in the posterior third ventricular region, but without any associated hydrocephalus which could explain her stuporous state. Given the rapid decline in her sensorium, we were faced with the difficult choice between surgical decompression of the tumor and a trial of rescue chemotherapy following histopathological confirmation through biopsy. She underwent an open biopsy followed by chemotherapy in a neurosurgical intensive care unit despite her poor Karnofsky performance score. She improved after chemotherapy and her tumor decreased in size significantly over time. We highlight the role of chemotherapy administered in the neurosurgical ICU to an unconscious patient with a large chemoresponsive tumor leading to rapid shrinkage of the lesion and gradual improvement in the sensorium of the patient.

Abstract Introduction: Breast cancer in India is phenotypically different with locally advanced breast cancers (LABCs) forming 30-50% of all cases. Use of neoadjuvant chemotherapy (NACT), among other things has contributed to surgeons using breast conservation surgery (BCS) in very selected patients with good results. Herein, we describe the oncological outcomes of BCS in LABC patients undergoing surgery post NACT. Patients and Methods: This is an ambispective observational cohort study conducted between January 1996 and December 2019 after approval by Institute Ethics Committee, to study the ipsilateral breast tumor recurrence (IBTR) in patients with LABC undergoing BCS post NACT. The secondary objectives were to ascertain the disease-free survival (DFS) and overall survival (OS) and factors associated with IBTR in these patients. Patients were staged according to the anatomic American Joint Committee on Cancer (AJCC) VIII Tumor Node Metastasis (TNM) classification and clinic-demographic, pathologic, treatment, and follow-up details were noted. Results: Out of 822 patients with LABC, 71 patients undergoing BCS post NACT were included. Average tumor size at presentation was 6.43 cm. The most common T stage was T3 (57.7%) and N stage was N1 (53.5%). The most common stage group was IIIB in 40.8%. Around 75% received anthracycline-based NACT with 28.2% having a complete clinical response. A pathological complete response was seen in 16 patients (22.5%). The mean follow-up duration was 6.14 years. A total of 25 patients had recurrences: five patients had IBTR (7%) and four had a local with regional recurrence. Two, 5, and 10 years OS were 94.0, 83.8, and 61.9%, respectively, and DFS were 87.8, 67.1, and 50.6%, respectively. A higher clinical T stage was associated with poor DFS (p = 0.01). The risk of IBTR was not found to significantly correlate with any of the standard prognostic factors. Conclusion: BCS post NACT in suitably selected patients of LABC is a safe and viable option without adversely affecting oncological outcomes.

Aim: Glioblastoma (GBM) is one of the most aggressive neoplasms of the central nervous system with dismal survival. In recent years, different variants of GBM have been described in the literature. GBM with areas of neuroectodermal differentiation (GBM-PNET) is a relatively new entity in GBM. Presence of the neuroectodermal component increases the propensity of systemic dissemination as with other intracranial primitive neuroectodermal tumors (PNET). The optimal treatment for these patients remains a controversy, with authors reporting local radiotherapy to craniospinal irradiation and chemotherapy. We intend to analyze the pattern of care for GBM with neuroectodermal component. Materials and Methods: We retrieved data of four patients with GBM-PNET treated in our institute; data were also retrieved from published series to derive treatment and outcome results. Results: In this series, we report the outcome of a series of four patients of GBM-PNET treated with adjuvant radiotherapy and temozolomide. All but one patient underwent gross total resection of the tumor. Adjuvant hypofractionated radiation with concurrent and adjuvant temozolomide was used in all cases. The median follow-up was 12.9 months in the present series. One patient experienced local recurrence 18 months after the treatment. A review of published literature on GBM-PNET was done; studies with details of patient outcome were used for an independent analysis. Twenty-three patients were identified, and the pooled analysis revealed a median progression free and overall survival of 10 and 25, months respectively. Extent of surgery, local radiation vs. craniospinal irradiation, and age at presentation had no impact on the survival. Conclusion: GBM PNET is a new entity with only few cases reported so far. Clinical behavior and treatment outcome of these tumors are not different from conventional GBM. However, these patients are at higher risk of CSF dissemination. Hence, an individualized treatment approach is best suited.

Background: Prostate cancer is a common cancer found in men worldwide. Brachytherapy is an established modality used for the treatment of these patients. Although anesthetic management of such patients is challenging but the ideal anesthetic technique has not yet been established. Our study aims to identify the most efficacious anesthetic technique for perioperative management of prostate cancer patients undergoing brachytherapy. Methods: Retrospective analysis of ten patients who underwent 16 brachytherapy sessions under combined spinal epidural (CSE) anesthesia between April 2016 and December 2016 was done. The data were collected, tabulated using MS Excel, and statistically analyzed with EPI Info 6 and SPSS-16 statistical software (SPSS Inc. Chicago, USA) to draw relative conclusions. Results: The median peak sensory dermatome level achieved was T6 and the median maximum motor block achieved was grade 2. The mean (± standard deviation (SD)) time to sensory regression to T10 (range T5-T8) dermatome was found to be 118.00 ± 47.110 (range = 0-238) minutes. Despite the presence of co-morbidities, minor intraoperative complications were observed only in two patients. The postoperative numerical rating scale (NRS) was less than 4 in all patients during the first 24 hours. None of our patients complained of nausea, vomiting, pruritus and respiratory depression. The mean (± SD) patient satisfaction score was 44.40 ± 0.871 (range : 1-5) at the end of 24 hours. Conclusions: CSE anesthesia is a safe and effective technique for anesthetic management of patients undergoing prostate brachytherapy.

BACKGROUND: Triple-negative breast cancers (TNBCs) are known for early age at presentation, large tumor sizes, and overall poor prognosis. However, Indian studies are scarce with limited follow-up data. Hence, the present study is aimed at characterizing nonmetastatic TNBC patients in our population and comparing their outcome with non-TNBC subset. METHODOLOGY: This is a retrospective observational study of nonmetastatic breast cancer patients accrued over 14 years. The demographic, clinical, and pathological profiles of TNBCs and their patterns of recurrences and survivals were compared to that of non-TNBC. Overall and disease-free survival (DFSs) were calculated from the time of initiation of therapy to the occurrence of event, i.e., death or recurrence. RESULTS: TNBC constituted 21.8% of all patients. Patients with triple-negative subtype were significantly younger and more likely to be premenopausal. Higher proportion of TNBC presented in locally advanced stage and had a higher proportion of node-positive patients compared to their non-TNBC counterparts. Although taxane-based neoadjuvant therapy was associated with significantly higher pathological complete responses, recurrences occurred earlier in TNBC. Even though inferior overall and DFSs were encountered in TNBC, statistical significance could not be derived. CONCLUSIONS: TNBCs are a subset of tumors with a poorly understood tumor biology and behavior. Despite being labeled as having an aggressive tumor biology and behavior, not many differences are seen in their clinical outcomes when they present as locally advanced cases.

The tumor was positive for the estrogen receptor and human epidermal growth factor receptor 2 and negative for progesterone receptor on immunohistochemistry. Follow-up contrast-enhanced computed tomography scan of the neck, chest, abdomen, and pelvis and contrast-enhanced magnetic resonance imaging of the brain were done in June 2016 which showed metastatic lesions in the brain, both lungs, bone, bilateral adnexae, and a well-defined mass (7.2 cm × 6.4 cm) in the right upper lobe of the lung with broad base toward costal pleura and medially abutting the superior vena cava [Figure 2]. Biopsy from this right upper lobe lung mass was done which showed a malignant spindle-cell tumor immunopositive for vimentin, desmin, MIC2, and EMA (focal weak) while negative for spinal muscular atrophy (SMA), CD34, myogenin, Bcl2, calretinin, and cytokeratin (CK) [Figure 1]b. Hence, she was placed on the second-line palliative chemotherapy with lapatinib and vinorelbine and also received palliative radiotherapy to the right lung mass (20 Gy/5 fractions over 1 week).

Giant cell glioblastoma (GCG) is a rare subtype of classic glioblastoma multiforme with favorable prognosis and little is known about its metastatic potential. We hereby present a unique case of GCG in a 7-year-old child who developed spinal and spinal leptomeningeal metastasis during adjuvant therapy. She succumbed to it in spite of salvage therapy.

Endolymphatic sac tumor (ELST) is a rare papillary neoplasm with locally destructive behavior which can occur sporadically or in association with Von Hippel-Lindau (VHL) disease. We herein present a case of ELST associated with VHL disease in a 14-year-old girl and discuss clinico-radiological, immunohistopathologic findings, and management by staged surgery and postoperative radiotherapy to the residual lesion.