A phase II study of neoadjuvant chemotherapy followed by organ preservation in patients with muscle-invasive bladder cancer.

Objective: Conservative approaches in muscle-invasive bladder cancer (MIBC) have been evolved to avoid aggressive surgery, but are limited to elderly, frail, and patients medically unfit for surgery. Our study aimed to assess the response rate of neoadjuvant chemotherapy (NACT) before radiotherapy (RT) in MIBC patients. Methods: Forty patients with urothelial carcinoma of stage T2-T4a, N0, M0 were enrolled between November 2013 and November 2015, and treated with three cycles of NACT with gemcitabine-cisplatin. Post-NACT response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Patients who achieved complete response (CR) and partial response (PR) >50% were treated with radical RT, and those who had PR <50%, stable disease (SD), and progressive disease (PD) underwent radical cystectomy (RC). Survival analysis was done with Kaplan-Meier method and point-to-time events were analyzed with Cox-proportional hazards regression model. Results: After NACT, 35 (87.5%) patients achieved either PR >50% or CR, and were treated with RT. Five (12.5%) patients who had PR <50%, SD, or PD underwent RC. All patients who received radiation showed CR after 6 weeks. Median follow-up was 43 months (range: 10-66 months) and median overall survival (OS) was not reached. Three-year OS, local control, and disease-free survival were 70.1%, 60.9%, 50.6%, respectively, and 50% of patients preserved their functioning bladder. Three-year OS rate was 88.9% in patients who achieved CR to NACT, 73.1% in patients with PR ≥50% and 40% in patients with PR <50%. Conclusion: NACT followed by RT provides a high probability of local response with bladder preservation in CR patients. Appropriate use of this treatment regimen in carefully selected patients may omit the need for morbid surgery.

Prognostic Value of HPV Infection Assessed by p16 Immunohistochemistry and the Influence of Tobacco Usage in Oropharyngeal Cancers: Real World Scenario.

To find if an association could be established between Human Papilloma Virus (HPV) infection and oropharyngeal cancers (OPCs) in a group of patients known to be regular users of tobacco, and to determine the impact of HPV status on clinical outcomes.Case records of 212 patients with AJCC-7 (The American Joint Committee on Cancer 7th edition) stages II-IVB non metastatic squamous cell carcinoma of the oropharynx treated using radical radiotherapy with or without chemotherapy during the years 2015-2018 were retrieved. Formalin-fixed, paraffin-embedded blocks from oropharyngeal biopsies were available for 177 patients and were evaluated for p16 expression by immunohistochemical (IHC) staining. More than 50% nuclear staining with or without cytoplasmic staining was considered HPV+ . The association between tobacco use and HPV, as well as the influence of HPV status on survival outcomes were assessed. p16 expression was found to be positive in 23(13%) patients. Significant association was found between chewable tobacco usage and HPV positivity (p = 0.051). The median follow up was 20.5 months (range: 3-80). 5-year Overall Survival was 43.4% and 29.8% (p = 0.044) in HPV+ and HPV- patients, respectively. Local control was significantly better in HPV+ patients (38.6% vs. 25.3%, p = 0.049). There was also a trend towards improved Disease-free Survival in HPV+ patients (31 months vs. 15 months, p = 0.078). Though less in prevalence among the Indian population, improved outcomes in HPV+ OPC patients and widely available IHC HPV assays signifies the routine implementation of p16 testing in day-to-day clinical practice.

Multimodality treatment for Central Nervous System Germ Cell Tumors: Disease spectrum and management strategies - A tertiary care center experience from India.

OBJECTIVE: Intracranial germ cell tumors (GCTs) are relatively rare neoplasms, representing 2-3 % of paediatric brain tumors in Western countries and 8-15 % in East Asia. Here, we discuss the clinical features and treatment outcomes in patients with central nervous system (CNS) GCTs treated at our institute. METHODS: Medical records of all primary CNS GCT patients were retrieved retrospectively from 2007 to 2019. Demographic, clinical, treatment and follow up details were entered in a predesigned proforma. Overall survival (OS) and progression-free survival was computed using Kaplan-Meier method and Log-Rank test. Effect of various prognostic factors on survival outcomes was assessed by univariate and multivariate analysis. RESULTS: A total of 28 CNS GCT patients were included in this analysis. Median age at presentation was 17 years (range, 7-45 years) with a male to female ratio of 1.8:1. Pineal region was the commonest location, encountered in 15 patients (53.6 %). Pure germinoma was the most frequent histology observed, seen in 19 patients (67.9 %). Male gender and germinoma histology were highly associated with pineal location (p = 0.043 and p = 0.052, respectively). Fourteen patients underwent surgical intervention and nine patients underwent biopsy for diagnostic purpose or to relieve the obstructive symptoms. Only 23 patients (82.1 %) received chemotherapy. However, all patients received radiotherapy (Craniospinal irradiation/whole brain radiotherapy/whole ventricular radiotherapy/ or local radiotherapy). After a median follow-up of 53 months (range, 7-150), 23 patients (82.1 %) were alive. OS was significantly affected by histology (89 % in germinoma vs. 60 % in non-germinomatous, p = 0.054) and location (93 % in pineal region vs. 64.2 % in other location, p = 0.042). Age, gender and surgery did not have any impact on the survival outcomes. CONCLUSION: CNS GCTs are relatively rare and heterogeneous neoplasms commonly seen in pineal and suprasellar locations. A combination of chemotherapy and radiotherapy had shown excellent outcomes.

Clinical Outcomes and Prognostic Factors in Gastric Carcinoma Patients with Curative Surgery Followed by Adjuvant Treatment: Real-World Scenario.

BACKGROUND: A wide range of adjuvant treatment regimens exist in gastric carcinoma patients which include chemotherapy, radiotherapy, and/or both either sequential or concurrent. The study aimed to assess the benefit of adjuvant sequential chemotherapy followed by radiotherapy for operable gastric cancers and evaluate the prognostic factors associated with clinical outcomes. METHODS: Patients of stage IB-III gastric carcinoma who underwent radical surgery followed by adjuvant treatment from January 2013 to December 2016 were analyzed retrospectively. Survival was computed using Kaplan-Meier method and prognostic factors were analyzed in multivariate analysis using Cox progression hazard model. A P value < 0.05 was taken as statistically significant. RESULTS: A total of 108 patients were identified with a median follow-up of 31.7 months (range: 6-96). Seventy-two percent of the patients received adjuvant sequential chemoradiation (N = 77) and 28% of patients received chemotherapy alone. The median survival was 26 months (95% CI: 23.09-28.90). Overall survival (OS) rates for 1, 2, 3, 4, and 5 years were 88.9%, 57.4%, 40.7%, 28.8%, and 20.4%, respectively. Five-year OS for stage-IB, II, and III was 75%, 45%, and 8.3%, respectively (p = 0.023). Surgical margin positivity (9.5% vs. 26.9%, p = 0.042), signet-ring cell histology (6.5% vs. 25.8%, p = 0.00), and adjuvant sequential chemoradiation (p = 0.002) showed a significant impact on survival outcomes and proved as independent prognostic factors. CONCLUSION: The present study demonstrated that survival in gastric carcinoma is influenced by the stage of disease and surgical margins. In locally advanced patients, radical surgery followed by sequential chemoradiation based on a doublet/triplet regimen was an independent prognostic factor for survival. Majority of patients in our set-up presented in locally advanced stage, curative resection followed by adjuvant sequential chemoradiation was an independent prognostic factor for survival.

Primary mediastinal germ cell tumors: Survival outcomes and prognostic factors - 10 years experience from a tertiary care institute.

Primary Mediastinal Germ Cell Tumor (PMGCT) is a rare and heterogeneous entity. These tumors are typically diagnosed in young adults and carry a poor prognosis. We conducted this study to evaluate the role of radiotherapy on treatment outcomes and prognostic factors in PMGCT that may allow a more adapted treatment strategy to improve survival. Case records of patients who presented with PMGCT over a period of 10-years from January-2009 to December-2019 were retrospectively evaluated. Survival analyses were calculated using Kaplan-Meier (Log-rank) method. Poor prognostic factors for survival were evaluated with Multivariate analysis using Cox-regression method. A total of 46-patients data was analyzed, the majority of the patients were males (95.7%) with a median age of 25-years (range, 17-62). Non-seminomatous histology was predominant (60.9%). Sixteen-patients (34.7%) presented with complications at their initial presentation. Majority of the patients were treated with multimodality approach using chemotherapy, surgery, and/or radiotherapy. At a median follow-up of 40.8 months, the 1, 3, and 5-year overall survival (OS) was 69.6%, 52.2%, and 44.7% respectively. Patients who received radiotherapy in first-line treatment showed significant improvement in 5-year OS (72% vs 30%, p = 0.004) and disease-free survival (70% vs 24%, p = 0.007) in comparison with patients who did not receive. Multivariate analysis revealed that radiotherapy, chemotherapy, surgery, and complications at presentation were independent prognostic factors for OS. PMGCTs are aggressive neoplasms especially in patients presenting with disease-related complications. Dual modality management (radiotherapy as local therapy along with chemotherapy) had shown improvement in survival.

Primary broad ligament adenocarcinoma.

Primary broad ligament carcinoma is a very rare occurrence with 28 reported cases worldwide, to date. The epidemiology, treatment strategy and prognosis are still uncertain because of the scarcity of cases. Currently, all broad ligament carcinomas are managed similar to epithelial ovarian cancer. We report the case of a 43-year-old female with a prolonged complaint of abdominal pain and intermittent urinary retention, requiring frequent catheterization. She was diagnosed with obstructive right hydroureteronephrosis. The abdominal Contrast Enhanced Computed Tomography (CECT) revealed a well-defined heterogeneous lesion of 2.1х3х3.2cm size in the right lateral and posterior wall of the cervix. An ultrasound (USG)-guided Fine Needle Aspiration Cytology (FNAC) of the mass was done and it was suspected to be malignant. The patient underwent total abdominal hysterectomy, right salpingo-oophorectomy, pelvic lymph-nodal sampling, and peritoneal washing. Histological examination depicted an endometrioid adenocarcinoma of the broad ligament. She received adjuvant chemotherapy, followed by hormonal therapy. It has been five years since her surgery, and she is now alive and disease free.

Erectile dysfunction and cancer: current perspective.

Erectile dysfunction (ED) is one of the major but underreported concerns in cancer patients and survivors. It can lead to depression, lack of intimacy between the couple, and impaired quality of life. The causes of erectile dysfunction are psychological distress and endocrinal dysfunction caused by cancer itself or side effect of anticancer treatment like surgery, radiotherapy, chemotherapy and hormonal therapy. The degree of ED depends on age, pre-cancer or pre-treatment potency level, comorbidities, type of cancer and its treatment. Treatment options available for ED are various pharmacotherapies, mechanical devices, penile implants, or reconstructive surgeries. A complete evaluation of sexual functioning should be done prior to starting anticancer therapy. Management should be individualized and couple counseling should be an integral part of the anticancer treatment.

Primary broad ligament adenocarcinoma

Primary broad ligament carcinoma is a very rare occurrence with 28 reported cases worldwide, to date. The epidemiology, treatment strategy and prognosis are still uncertain because of the scarcity of cases. Currently, all broad ligament carcinomas are managed similar to epithelial ovarian cancer. We report the case of a 43-year-old female with a prolonged complaint of abdominal pain and intermittent urinary retention, requiring frequent catheterization. She was diagnosed with obstructive right hydroureteronephrosis. The abdominal Contrast Enhanced Computed Tomography (CECT) revealed a well-defined heterogeneous lesion of 2.1х3х3.2cm size in the right lateral and posterior wall of the cervix. An ultrasound (USG)-guided Fine Needle Aspiration Cytology (FNAC) of the mass was done and it was suspected to be malignant. The patient underwent total abdominal hysterectomy, right salpingo-oophorectomy, pelvic lymph-nodal sampling, and peritoneal washing. Histological examination depicted an endometrioid adenocarcinoma of the broad ligament. She received adjuvant chemotherapy, followed by hormonal therapy. It has been five years since her surgery, and she is now alive and disease free.

Platinum sensitive carcinoma of ovary relapsed as pericardial effusion with cardiac tamponade.

Epithelial ovarian cancers typically spread by intraperitoneal exfoliation and retroperitoneal lymph nodal involvement along the ovarian vascular supply. Pericardial involvement in ovarian malignancies is very rare with only few cases reported in the literature. Malignancy is the most common cause for pericardial effusion in the western world. In this case report, we present a 58-year-old woman treated for high-grade serous carcinoma of the ovary in 2010, relapsed with pericardial effusion and cardiac tamponade in 2017. Imaging studies revealed gross pericardial effusion. Two-dimensional echocardiogram showed massive pericardial effusion, with cardiac tamponade, New York Heart Association-IV. Pericardiocentesis and pigtail drain was placed under echo guidance. Immunocytochemistry has confirmed the tumour cells to be of the ovarian origin. The patient underwent surgical pericardial window via thoracotomy, followed by paclitaxel and carboplatin-based chemotherapy and olaparib maintenance.

Analysis of volumetric and dosimetric changes in mid treatment CT scan in carcinoma nasopharynx: implications for adaptive radiotherapy.

OBJECTIVE: Carcinoma of nasopharynx is a radiosensitive tumor and therapeutic response during radiation treatment can result in dosimetric variations in the delivered dose to the tumor and critical organs. This study was done to evaluate the volumetric and dosimetric changes seen in tumor tissue and organs at risk in a mid treatment planning scan and its implications for adaptive replanning. Twenty patients of locally advanced carcinoma nasopharynx were evaluated. All patients were started on treatment with a baseline treatment plan on SIB-VMAT. To evaluate volumetric and dosimetric changes during treatment, a mid treatment CT scan (MTS) was taken at the 17th fraction of treatment and compared with the baseline planning CT scan (BS). Adaptive treatment plans were generated on the MTS and further treatment was continued on the adaptive plans. The mean weight loss observed at the 17th fraction of treatment was 3.4 ± 2.6 kg(Mean±S.D). The mean neck diameter at C2 level was 14.19±1.02 and 13.29 ± 1.14 cm in the BS and MTS respectively (p=0.001). The GTV 70 volume showed a 29.16% volume loss. The mean doses received by the right and left parotids were 25.45±0.98 and 24.64±3.8 Gy in the baseline treatment plan and 33.21±11.29 (p=0.054) and 31.76±8.44 Gy respectively in the MTS (p=0.016) The mean weight loss showed a statistically significant correlation with increase in the right parotid(p=0.043) and left parotid doses(p=0.024). Weight loss during treatment combined with volume changes in target tissues mandate routine adaptive replanning while treating carcinoma nasopharynx.

Toxicity and clinical outcomes with definitive three-dimensional conformal radiotherapy (3DCRT) and concurrent cisplatin chemotherapy in locally advanced cervical carcinoma.

OBJECTIVE(S): This study aimed to retrospectively evaluate the toxicity and clinical outcomes in patients of locally advanced cervical cancer treated with three-dimensional conformal radiotherapy (3DCRT) and concurrent chemotherapy. MATERIAL AND METHODS: Two hundred and ten newly diagnosed patients of locally advanced cervical cancer of FIGO 2009 Stage II-III treated with 3DCRT (46 Gy/23 fractions/4½ weeks) and weekly concurrent Cisplatin (40 mg/m2), from January 2013 to 2015 were analyzed. A planning computed tomography was performed and contouring was done according to published guidelines. External radiotherapy was followed by Intracavitary brachytherapy delivered to a dose of 9 Gy HDR in 2-fractions, given one week apart. The endpoints were treatment related toxicities and clinical outcomes. Local control (LC), overall survival (OS) and disease free survival (DFS) were evaluated and toxicities were documented using the common terminology criteria for adverse events (v3.0) (CTCAE). RESULTS: The median follow up time was 37 (range, 19-54) months. The 3 year OS, DFS and LC were 84.2%, 80.6% and 81% respectively. Grade ≥3 acute skin, upper and lower gastrointestinal (GI) and genitourinary (GU) toxicity was observed in 3 (1.4%), 11 (5.2%), 12 (5.7%) and 0 (0%) patients, respectively. Grade ≤2 hematological toxicity was observed in 154 (73.3%) patients. Grade ≥3 late GI and GU toxicity was seen in 9 (4.2%) patients and 2 (0.9%) patients, respectively. CONCLUSION: 3DCRT with concurrent chemotherapy results in good loco-regional control with acceptable normal tissue toxicity. In the background of indeterminate evidence regarding routine practice of intensity modulated radiotherapy in carcinoma of the cervix, 3DCRT may be considered as the treatment of choice.

Radiation induced secondary malignancies: a review article.

Radiation-induced second malignancies (RISM) is one of the important late side effects of radiation therapy and has an impact on optimal treatment decision-making. Many factors contribute to the development of RISM such as age at radiation, dose and volume of irradiated area, type of irradiated organ and tissue, radiation technique and individual and family history of cancer. Exact mechanism of RISM is unknown. But nowadays, it is a growing concern in oncology because of the increased number of cancer survivors and efforts are being made to prevent or decrease the incidence of RISM. The primary search for articles was carried via Google Scholar and PubMed with keywords included 'radiation induced malignancies, second malignancies, and chemotherapy induced malignancies'. Additional papers were found through references from relevant articles. In this review article, we have discussed about the pathogenesis, factors contributing to RISM, screening and prevention strategies of RISM.