A qualitative study to assess the psychological experiences and coping strategies of families affected with Li-Fraumeni syndrome in the Indian population.

Background: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant hereditary cancer syndrome. Due to the high risk of occurrence of multiple cancers, families with LFS may have an overwhelming psychosocial burden. Methods: This cross-sectional study was conducted at a tertiary care center using face-to-face interviews through a grounded theory approach. Statistical analysis was done using Smith's Interpretative Phenomenological Approach. Themes and sub-themes were extracted, and a thematic schema was developed. Results: A total of five themes were identified. The extracted themes were psychological experiences, behavioural responses, stressors, coping strategies and perceived needs. The interlay of the themes deepened the impact of LFS on the affected ones and brought into light the turmoil of emotions and difficulties that these individuals were going through in the face of the disease. Conclusions: LFS-affected individuals had a range of experiences with this rare and little-known disease. The lack of information seems to be a precursor to the denial of diagnosis. Their experience with the illness sheds light on the grey areas like guilt and helplessness that demand immediate attention. Future policies need to be developed in accordance with the identified perceived needs to potentially guide the treatment and rising needs of LFS-affected individuals.

A phase II study of gemcitabine and docetaxel combination in relapsed metastatic or unresectable locally advanced synovial sarcoma.

Synovial sarcoma (SS) is one of the commonest non-rhabdomyosarcoma soft tissue sarcoma with limited treatment options in the relapsed and advanced settings. The combination of gemcitabine and docetaxel has demonstrated its role predominantly in leiomyosarcoma and pleomorphic sarcomas but has not been prospectively studied in SS. This trial assesses the efficacy, tolerability and quality of life (QoL) with this regimen in metastatic/unresectable locally advanced relapsed SS.Patients and methods This was a single-arm, two-stage, phase II, investigator-initiated interventional study among patients with metastatic or unresectable locally advanced SS who had progressed after at least one line of chemotherapy. Gemcitabine 900 mg/m2 on days 1 and 8 and docetaxel 75 mg/m2 on day 8 were administered intravenously every 21 days. The primary endpoint was 3-month progression-free rate (PFR); overall survival (OS), progression-free survival (PFS), overall response rate (ORR), safety and quality of life (QoL) constituted the secondary endpoints.Results Twenty-two patients were enrolled between March 2020 and September 2021 and the study had to be closed early due to slow accrual. The study population comprised of 18 (81.8%) patients with metastatic disease and 4 (18.2%) patients with locally advanced, unresectable disease. The most common primary sites of disease were extremity in 15 (68%) and the median number of lines of prior therapies received was 1 (range 1-4). 3-month PFR was 45.4% (95% CI 24.8-66.1) and ORR was 4.5%. Median progression-free survival (PFS) was 3 months (95% CI 2.3-3.6) and median OS was 14 months (95% CI 8.9-19.0). 7 (31.8%) patients experienced grade 3 or worse toxicities, including anemia (18%), neutropenia (9%) and mucositis (9%). QoL analysis demonstrated significant decline in certain functional and symptom scales, while financial and global health scales remained stable.Conclusion This is the first prospective study on the combination of gemcitabine and docetaxel performed specifically in patients with advanced, relapsed SS. Although the accrual of patients could not be completed as planned, the therapy did produce clinically meaningful outcomes and met its primary endpoint of 3-month PFR. This result, along with the manageable toxicity profile and stable global health status on QoL analysis, should encourage further studies.Trial registration This trial was prospectively registered under the Clinical Trials Registry of India on 26/02/2020 (Registration number: CTRI/2020/02/023612).

Lessons learnt from the clinico-genomic profiling of families with Li Fraumeni syndrome at a tertiary care centre in North India.

Li Fraumeni syndrome (LFS) is an inherited cancer predisposition syndrome due to TP53 gene mutation. There is sparse literature on LFS in the Indian population. We conducted a retrospective study of patients diagnosed with LFS and their family members, registered at our Medical Oncology Department between September 2015 and 2022. 9 LFS families consisted of 29 patients diagnosed currently or historically with malignancies including 9 index cases and 20 first or second-degree relatives. Of these 29 patients, 7 (24.1%) patients developed their first malignancy before the age of 18 years, 15 (51.7%) were diagnosed between 18and and 60 years, and 7 (24.1%) were diagnosed at age more than 60 years. A total of 31 cancers occurred among the families, including 2 index cases who had metachronous malignancies. Each family had a median of three cancers (range 2-5); sarcoma (n = 12, 38.7% of total cancers) and breast cancer (n = 6, 19.3% of total cancers) being the commonest malignancies. Germline TP53 mutations were documented among 11 patients with cancers and 6 asymptomatic carriers. Of these nine mutations, the most common types were missense (n = 6, 66.6%) and nonsense (n = 2, 22.2%), and the commonest aberration was replacement of arginine with histidine (n = 4, 44.4%). Eight (88.8%) families met either classical or Chompret's diagnostic criteria and two (22.2%) satisfied both. Two (22.2%) families fit the diagnostic criteria prior to onset of malignancy in the index cases but were untested till the index cases presented to us. Four mutation carriers from three families are undergoing screening as per the Toronto protocol. No new malignancies have been detected so far during the mean surveillance duration of 14 months. The diagnosis of LFS has socio-economic implications for patients and their families. Delay in genetic testing misses out a crucial window wherein asymptomatic carriers could initiate surveillance in a timely fashion. Greater awareness on LFS and genetic testing in Indian patients is warranted for better management of this hereditary condition.

Autologous stem cell transplant for multiple myeloma: Impact of melphalan dose on the transplant outcome.

We evaluated impact of melphalan dose on transplant outcomes for multiple myeloma. Between 1995 and 2019 459 consecutive patients received a transplant; 69(15%) received melphalan ≤150 mg/m2 (Mel 150 cohort) and 390 (85%) melphalan 200 mg/m2 (MEL 200 cohort). The primary outcome was overall survival (OS) from the date of transplant. Progression-free survival (PFS), engraftment, transplant response, and cumulative relapse at 2 years were secondary outcome measures. Patients in Mel 150 cohort had adverse clinical and laboratory parameters at base line. Transplant response was better for Mel 200 cohort (p < 0.024). Median OS at a median follow-up of 88 months was similar in the two cohorts; 100 Vs 102 months (Mel 200), p = 0.817. Median PFS (60.0 Vs 53 months, p = 0.746), relapse at two years (32.4% Vs 30.9%, p = 0.745) and grade 3-4 mucositis (p = 0.823) were similar. Initial treatment prepares patients better for subsequent similar transplant outcomes despite differences in baseline characteristics.

Management and outcomes of advanced hemangioendothelioma at a medical oncology clinic in an Indian tertiary care center.

Aim: Hemangioendotheliomas (HEs) are malignant vascular tumors with sparse descriptions in literature owing to their rarity. Study design: Ours is a retrospective study among patients of advanced HEs registered between September 2015 and April 2021. Results: There were 13 patients with median age 34.6 (range: 4-69 years), male preponderance (69%) and predominant subtype of epithelioid HE (76.9%). Common primary sites were viscera (46.2%) and bone (30.8%). Tyrosine kinase inhibitors (TKIs) yielded objective responses in 30% patients whereas chemotherapy only produced disease stabilization in 7.7%. Conclusion: We recognize an aggressive subset of HEs with manifestations such as acute liver failure and splenic rupture. Currently no biomarkers predict the efficacy of TKIs over chemotherapy; however, TKIs showed promising outcomes in this series.

Hemangioendotheliomas are rare malignant tumors with vascular origin. This retrospective study on 13 patients displays a male preponderance, the with epithelioid subtype being the commonest in the study population. The disease also showed aggressive manifestations such as acute liver failure and ruptured spleen. The viscera and bone were the commonest primary locations in 46.2 and 30.8% patients, respectively. Treatment with tyrosine kinase inhibitors showed a promising 30% response rate while chemotherapy showed stabilization of disease in 7.7% patients.

Carney's triad in an adult male from a tertiary care center in India: a case report.

BACKGROUND: Carney's triad is a rare syndrome comprising gastrointestinal stromal tumor, extra-adrenal paraganglioma, and pulmonary chondroma along with newer additions of adrenal adenoma and esophageal leiomyoma. The triad is completely manifest in only 25-30% cases, with most patients presenting with two out of three parts of the syndrome. Wild-type succinate-dehydrogenase-deficient gastric gastrointestinal stromal tumor forms the most common component of Carney's triad and is usually multicentric and multifocal. It usually demonstrates indolent behavior and resistance to imatinib; hence, the management remains predominantly surgical. Pulmonary chondromas are commonly unilateral and multiple with slow-growing nature, which allows for conservative management. Adrenocortical adenomas are found in 20% of patients and are usually detected as incidentalomas. CASE PRESENTATION: A 49-year-old Asian male presented with upper gastrointestinal bleed and was diagnosed with multiple gastric succinate-dehydrogenase-deficient gastrointestinal stromal tumors. On evaluation, he was found to have left pulmonary chondroma and non-secretory adrenal adenoma, thus completing the Carney's triad. He underwent surgery with sleeve gastrectomy and excision of the antral tumor nodule, while the adrenal and pulmonary tumors have been under close follow-up. CONCLUSION: Literature regarding Carney's triad is scarce, especially from the Indian setting. Our report aims to highlight the various manifestations of this syndrome with emphasis on management of wild-type succinate-dehydrogenase-deficient gastrointestinal stromal tumor. Radical gastric surgeries do not offer a survival advantage in this condition; hence, more conservative modalities of resection can be adopted.

Early clinical and metabolic response to tazemetostat in advanced relapsed INI1 negative epithelioid sarcoma.

Epithelioid sarcoma (ES) is a rare soft tissue sarcoma with an incidence of 0.05 per 100,000 population in the USA. It is characterized by multiple local recurrences and regional lymph nodes form the commonest site of metastases. The function of Integrase Inhibitor 1 (INI1) protein is lost in more than 90% of cases, which was the basis for the introduction of tazemetostat into the therapeutic armamentarium for management of advanced ES. The efficacy and manageable toxicity profile of tazemetostat have been demonstrated recently, leading to its accelerated approval for treatment of advanced ES. We report one of the first real-world cases of relapsed, metastatic ES treated with tazemetostat. The patient attained partial response with the therapy and is tolerating the drug well without serious toxicities.

Long lasting response with trabectedin monotherapy in relapsed metastatic mesenchymal chondrosarcoma.

BACKGROUND: Mesenchymal chondrosarcoma is an exceedingly rare malignancy, accounting for around 5% of all patients with chondrosarcoma. It is a translocation-related sarcoma that tends to have both local and distant recurrences. Surgery is the mainstay of treatment in localised cases however treatment of advanced cases remains a challenge. The rarity of the disease precludes dedicated clinical trials and hence guidelines for its management are not well defined. The dearth in literature makes it pertinent that the cases treated with newer therapies must be reported to contribute to existing knowledge. CASE PRESENTATION: We hereby report a case of a 39-year old male without any comorbidity presenting with pelvic pain and was diagnosed as mesenchymal chondrosarcoma of the pelvis. He underwent an initial curative resection followed by a disease-free interval of 7 months. Subsequently, he was treated with pulmonary metastatectomy and local debulking surgery at time of initial relapse. He was then exposed to multiple lines of palliative chemotherapy, which limited our treatment options upon subsequent disease progression. Based on recent data, the patient was given trabectedin monotherapy as fourth line chemotherapy. He tolerated the therapy well and attained a progression-free survival of 12 months, which is an impactful figure in relapsed setting in this patient population. CONCLUSION: This report aims to present a comprehensive review into available and newer treatment choices for mesenchymal chondrosarcoma, and to highlight trabectedin monotherapy as a possible therapeutic option for mesenchymal chondrosarcoma in the relapsed setting.

Case Report: Cardiac Tamponade in Dengue Hemorrhagic Fever: An Unusual Manifestation of a Common Disease.

Dengue hemorrhagic fever is one of the most commonly encountered mosquito-borne viral infections of humans worldwide with multiple reported outbreaks. Cardiac involvement is a known manifestation of the disease usually presenting as rhythm abnormalities, myocarditis, or pericardial effusion, which may be clinically asymptomatic. We describe a case of a 30-year-old woman who presented to us with high-grade fever, headache, retro-orbital pain, generalized maculopapular rash with bilateral pleural effusion, and hypotension. Dengue non-structural protein 1 (NS1) antigen and IgM antibodies were positive on admission, supporting a diagnosis of dengue hemorrhagic fever. Cardiac troponin-I was elevated on admission (65 ng/L) with diffuse convex ST segment elevations on electrocardiogram, suggestive of possible myopericarditis. Echocardiogram on admission revealed minimal pericardial effusion with preserved ejection fraction. Despite administration of fluids and inotrope use, the patient's hypotension progressively deteriorated over the next 6 hours, associated with decreased urine output and worsening sensorium. Clinical examination revealed muffled heart sounds and raised jugular venous pressure. A repeat echocardiogram confirmed an increase in the pericardial effusion manifesting as cardiac tamponade. Ultrasound-guided pigtail catheter insertion led to a prompt removal of the excessive pericardial fluid and correction of hypotension. Early identification of this uncommon but important complication of dengue hemorrhagic fever led to a good outcome in our case.

Disseminated mucormycosis: A sinister cause of neutropenic fever syndrome.

A 15 year old girl presented with complaints of prolonged fever and recurrent episodes of hemoptysis. Initial investigation showed pancytopenia and radiological imaging was suggestive of necrotizing pneumonia. Subsequently, mucor was isolated from bronchoalveolar lavage fluid, but even on appropriate medications her condition kept deteriorating. She had multiple bouts of hemoptysis and a repeat imaging of chest showed dissemination of mucormycosis to pulmonary vein and heart. Bone marrow biopsy identified acute lymphoblastic leukemia (ALL) as the cause of pancytopenia. She was planned for bronchial artery embolization and chemotherapy for ALL, but consent was not given and she left our institute against medical advice. Our case highlights the importance of keeping a high index of suspicion for disseminated mucormycosis in neutropenic patients, as any delay in diagnosis and treatment could have grave consequences.

Expanded dengue syndrome in secondary dengue infection: A case of biopsy proven rhabdomyolysis induced acute kidney injury with intracranial and intraorbital bleeds.

Dengue fever is endemic in the Indian subcontinent and can have myriad presentations. The term expanded dengue syndrome (EDS) is used for atypical manifestations in dengue fever. We present a rare case of EDS in a patient with secondary dengue infection who developed rhabdomyolysis induced acute kidney injury (RAKI) along with intracranial and intraorbital bleeds. Patient was successfully managed in our institute and was discharged in stable condition. To the best of our knowledge, this is the only reported case of simultaneous occurrence of these complications in a dengue patient. This case is being presented to make clinicians aware of the spectrum of dengue infection.

Left Pulmonary Agenesis with Right Lung Bronchiectasis in an Adult.

Pulmonary agenesis is a rare congenital anomaly characterized by the absence of pulmonary parenchyma and vasculature. Bilateral pulmonary agenesis is incompatible with extrauterine life. Unilateral agenesis is often associated with other congenital cardiovascular, genitourinary and gastrointestinal malformations. Right lung agenesis is more frequently associated with congenital anomalies and has poor prognosis as compared to left lung agenesis. Diagnosis is often made in childhood but can be delayed, if the clinician is not aware about this entity. Chest radiograph in unilateral lung agenesis shows opaque hemithorax and these patients are often confused with other common causes of opaque hemithorax like collapse, pleural effusion and diaphragmatic hernia. We report a case of left lung agenesis with right lung bronchiectasis in a middle-aged adult who was treated for tuberculous pleural effusion and was referred to our institute for persistent symptoms despite treatment.

Leukemoid Reaction in Chikungunya Fever.

Chikungunya is a viral illness caused by an arbovirus which is transmitted by Aedes mosquito. Fever and polyarthralgia are hallmark of this viral illness. Viral infections are generally associated with leucopenia and bacterial infections with leukocytosis. Leukemoid Reaction (LR) is defined by reactive increase in leukocyte count of more than 50,000/cu mm with increase in mature leukocytes on peripheral blood. Leukocytosis is common in Chikungunya but leukemoid reaction has not been reported in medical literature. Our patient presented with high grade fever and symmetrical polyarthritis. Blood investigation showed Leukemoid reaction and after extensive work up a diagnosis of chikungunya was made.