Zachariah Thomas

Purpose: Somatic-type malignancy (SM) of germ cell tumor (GCT) is rare but demonstrates aggressive behavior. Differences by primary site, time to transformation, and mutational status remains poorly characterized. Patients and Methods: We reviewed all SM patients from June 2016 - May 2025 at a tertiary referral center. Time to somatic transformation (TST) was defined from initial GCT diagnosis to SM detection. SM were classified based on time of detection- at initial diagnosis (de novo), at consolidative surgery, relapse under 5 years, and evolved SM- relapse after 5 years. Descriptive statistics, Kaplan–Meier estimates, and Cox regression analyses were used. Results: 72 patients were identified: 40 (56%) with testicular, 24 (33%) with mediastinal, and 8 (11%) with other primaries. 22/24 (92%) mediastinal tumors with SM had sarcomatous transformation. Sarcoma was seen in 25/42 (60%) of de novo SM while adenocarcinoma was detected as an evolved entity in 5/6 (83.3%) cases. Embryonic type neuroectodermal tumor (ENET) histology carried poor prognosis compared to non-ENET histology (median OS 1.8 vs 8 years; HR 1.94, p = 0.1). Genomic data available showed PTEN-AKT-mTOR pathway mutations (33%) and TP53 mutations (33%), enriched in extra-gonadal sarcomatous SM. Conclusions: SM exhibits temporal, histologic, and molecular distinctions across primary sites. Response to front-line therapy and survival outcomes are poor. Future direction includes the exploration of underlying predictors of transformation and identification of targetable alterations in the relapsed setting.

Immunotherapy has demonstrated activity in metastatic penile cancer. Shan and colleagues report encouraging safety, efficacy, and tolerability of perioperative chemoimmunotherapy in advanced disease. While these results are promising, they underscore the urgent need for randomized trials to define the role and timing of immunotherapy in this rare and lethal disease.

Skull base osteomyelitis (SBO) is a potent life-threatening infection that can be either otogenic, rhinogenic or odontogenic in origin. The characteristic features of this disease include severe nocturnal pain and cranial nerve palsies, thus causing severe morbidity and even mortality. Clinical data of 134 patients diagnosed with Skull base Osteomyelitis were retrospectively reviewed, and their demographic details, clinical features, surgical procedure, microbiolgical profile were analysed. In this cohort, 123 patients underwent targeted biopsy and debridement, which showed a male preponderance with a mean age of 60 and uncontrolled diabetes with a mean HbA1C of 8.4. The most common symptom was severe otalgia followed by facial nerve palsy. 85.4% of the patients were culture-positive and 14.6% were culture-negative. Pseudomonas spp was isolated in 32.6%, followed by Aspergillus spp (26%), Staphylococcus spp (25%) and atypical organisms (37%). The patients who underwent targeted biopsy and debridement followed by culture-specific antibiotics for appropriate duration showed 85% improvement in clinical symptoms with a significant improvement in culture positive group (p<0.05). SBO, a potent fatal infection, can be secondary to bacterial or fungal infection. Early diagnosis and targeted biopsy may yield a culture-positive rate of 84.6%. Treatment with long-term culture-specific antibiotics/antifungals has improved clinical outcomes.

PURPOSE: There is a lack of literature on treating stage III non–oncogene-driven non–small cell lung cancer (NSCLC) with low-dose immunotherapy in combination with chemotherapy for patients who are not candidates for local therapy up front. MATERIALS AND METHODS: We performed an institutional retrospective analysis of patients with stage III non–oncogene-driven NSCLC deemed ineligible for up-front local therapy. The NACT + I/O group comprised those who received induction chemotherapy in combination with low-dose nivolumab, and the NACT-alone group comprised those who received chemotherapy alone. Propensity score matching was performed based on stage, histology, and respiratory comorbid status. The primary end point was objective response rate (ORR). Secondary end points were conversion rates to local therapy, progression-free survival (PFS), overall survival (OS), and Grade ≥3 adverse events. RESULTS: Eighty-two patients were equally divided into the NACT + I/O and NACT-alone groups. The most common histology was squamous cell (60%), followed by adenocarcinoma (34%) and mixed (5%). Majority (85%) had stage IIIB or IIIC disease. The ORR to induction was 73.1% (complete response 1, partial response [PR] 29, stable disease [SD] 10, progressive disease [PD] 1) in the NACT + I/O group versus 39% (PR-16, SD-13, PD-12) in the NACT-alone group ( P = .002). The NACT + I/O group had a higher proportion of patients undergoing sequential local therapy (66% v 46.3%, P = .075), a better median PFS (not reached [NR] v 11 months, P = .0014), and median OS (NR v 28 months, P = .22) compared with the NACT-alone group at a median follow-up of 13.5 months. There were no new safety signals identified. CONCLUSION: Adding low-dose immunotherapy to chemotherapy improved ORRs, conversion rates to local therapy, and PFS in patients with stage III non–oncogene-driven NSCLC, who were ineligible for up-front local therapy.

Intestinal-type sinonasal adenocarcinoma is a rare epithelial malignancy primarily treated with surgery and chemoradiation. The combination of low-dose immunotherapy and a tyrosine kinase inhibitor in recurrent disease has not been previously studied. A man in his 20s with papillary adenocarcinoma of the sinonasal region, following surgical resection, was treated with six cycles of concurrent chemoradiotherapy, followed by four cycles of docetaxel, cisplatin and capecitabine. While on treatment, he was found to have extensive residual disease and he was started on low-dose nivolumab and cabozantinib. Repeat imaging after ten months of treatment revealed a significant reduction in lesions. Non-squamous head and neck cancers are often excluded from major trials, and the effect of immunotherapy in these histologies is poorly understood. The response seen with low-dose immunotherapy underscores the need for further research in this setting.

A BSTRACT: Context and Aim: Diabetes mellitus (DM) can affect one’s quality of life (QoL). Literature on the association of QoL among type II diabetics with drug compliance and diet quality among rural communities is poor. This study aimed to determine the QoL among those with type II DM attending an outpatient clinic at a secondary hospital in Tamil Nadu. Settings and Design: A cross-sectional, interview-based study was carried out among those with type II DM. A questionnaire comprising the WHO-BREF tool, Diabetes Healthy Eating Index, Hill-Bone Medication Adherence Scale was administered to participants selected via systematic random sampling. Results: The prevalence of good QoL was estimated to be 51.7% ( n = 45, 95% CI: 41.20–62.20). There was no association between good QoL and medication compliance. None of the patients had a good diet quality. Bivariate analysis revealed significant association ( p < 0.05) between good QoL and higher education (OR-2.70), those not on medication for complications (OR-2.81) and decreased frequency of general random blood sugar (GRBS) monitoring (OR-2.44). Multivariable analysis adjusting for gender, education, treatment/medication for complications, hospitalisation for DM and GRBS frequency demonstrated significant association between good QoL, lack of medication for complications/co-morbidities and decreased GRBS monitoring frequency with likelihood ratios of 3.25 and 3.44, respectively. Conclusions: The drop in QoL observed could be due to the aftermath of the COVID pandemic. Keeping in mind the impact of healthcare interventions on the QoL of type II DM patients, primary physicians must consider dietary and treatment plans suited to their socio-economic status.