Oncofertility and Pregnancy in Adolescent and Young Adult Cancers: Physicians' Knowledge and Preferences in India.

PURPOSE: The treatment outcomes of adolescent and young adult (AYA) cancers have improved with advanced oncology care. Hence, fertility preservation (FP) and post-therapy pregnancies (PTPs) become vital issues. MATERIALS AND METHODS: An online survey link with 17 questions regarding oncofertility and PTPs was circulated among oncologists to assess the knowledge, understand the oncofertility care patterns, and seek suggestions to improve oncofertility services. RESULTS: The median age of 179 respondents, predominantly medical oncologists (68.7%), was 37 years (IQR, 10; range, 29-74), working in academic centers (39%) having a median experience of 4 years (IQR, 4; range, 1-42); 23 (12.8%) had dedicated AYA cancer units. Although a quarter (19%-24%) of respondents discussed fertility issues in >90% of AYA patients with cancer, only a tenth (8%-11%) refer >90% for FP, with significantly higher (P < .05) discussions and referrals in males and by more experienced oncologists (P < .05). Forty-six (25.6%) were not well versed with international guidelines for FP. Most (122, 68.1%) oncologists knew about the referral path for semen cryopreservation; however, only 46% were knowledgeable about additional complex procedures. One hundred and ten (61.5%) oncologists never or rarely altered the systemic treatment for FP. Prominent barriers to FP were ignorance, lack of collaboration, and fear of delaying cancer treatment. Lead thrust areas identified to improve FP practices are education, and enhanced and affordable access to FP facilities. Seventy-four (41.3%) respondents knew about international guidelines for PTPs; however, only half (20%) of them often monitored fertility outcomes in survivors. Oncologists have conflicting opinions and uncertainties regarding pregnancy safety, assisted reproductive techniques, breastfeeding, and pregnancy outcomes among survivors. CONCLUSION: Oncologists are uncertain about the guidelines, FP practices, referral pathways, and PTPs. Multipronged approaches to improve awareness and provision for affordable oncofertility facilities are needed to enhance AYA cancer outcomes in India, which will be applicable to other low- and middle-income countries too.

Epidemiology of rare cancers in India and South Asian countries - remembering the forgotten.

Background: Rare cancers (RCs) are challenging to manage and are "forgotten cancers" though they collectively constitute a significant proportion of all cancers (∼20%). As a first step towards streamlining care, there is an unmet need to map the epidemiology of RCs in South Asian Association for Regional Collaboration (SAARC) countries. Methods: The authors collected data from 30 Population-Based Cancer Registries (PBCR) of India and the published national registries of Nepal, Bhutan and Sri Lanka (SL) and compared them with the standard RARECAREnet RC list. Findings: With the standard definition of crude incidence rates (CR) ≤6/100,0000 per population, 67.5%, 68.3%, 62.3% and 37% of all incident cancers qualify as RCs in India, Bhutan, Nepal and SL, respectively. An arbitrary cut-off CR ≤3 appears more appropriate with 43%, 39.5%, 51.8% and 17.2% of cancers identified as RCs, respectively, due to the lower cancer incidence.There are similarities and notable differences between the RC lists of the SAARC region with that of the European RC list. Oral cavity cancers are rare in Europe, while pancreas, rectum, urinary bladder and melanomas are common. In addition, uterine, colon and prostatic cancers are rare in India, Nepal and Bhutan. In SL, thyroid cancer is common. There are gender-related and regional differences in RC trends in the SAARC countries. Interpretation: There is an unmet need in SAARC nations to capture epidemiological nuances in rare cancers. Understanding the unique issues in the developing world may guide policymakers to adopt appropriate measures to improve RC care and tailor public health interventions. Funding: None.

Outcomes with chemotherapy in carcinoma penis: Experience from a tertiary cancer center.

Background: Carcinoma penis is more common in India compared to the West. The role of chemotherapy in carcinoma penis is ambiguous. We analyzed the profile and outcomes of patients with carcinoma penis treated with chemotherapy. Methods: We analyzed the details of all patients with carcinoma penis treated at our institute between 2012 and 2015. We collected particulars regarding demography, clinical presentation, treatment details, toxicities, and outcomes of these patients. Event-free and overall (OS) survival were calculated from the time of diagnosis until documentation of disease relapse/progression or death for the patients with advanced carcinoma penis who were eligible for chemotherapy. Results: There were 171 patients with carcinoma penis treated at our institute during the study period including 54 (31.6%) patients with stage I, 49 (28.7%) patients with stage II, 24 (14.0%) patients with stage III, 25 (14.6%) patients with stage IV, and 19 (11.1%) patients with recurrent disease at presentation. The present study included 68 patients with advanced carcinoma penis (stages III and IV) who were eligible for chemotherapy, with a median age of 55 years (range: 27-79 years). Sixteen patients received paclitaxel and carboplatin (PC) and 26 patients cisplatin and 5-FluoroUracil (CF). Neoadjuvant chemotherapy (NACT) was given to four patients with stage III and nine patients with stage IV disease. Of the 13 patients given NACT, we observed a partial response in five (38.5%), stable disease in two (15.4%), and progressive disease in five (38.5%) evaluable patients. Six (46%) patients underwent surgery after NACT. Only 28/54 (52%) patients received adjuvant chemotherapy. After a median follow-up of 17.2 months, the 2-year OS rates were 95.8, 89, 62.7, 51.9, and 28.6% for stages I, II, III, IV, and recurrent disease, respectively. The 2-year OS of patients who were given chemotherapy versus those who were not given chemotherapy were 52.7 and 63.2%, respectively (P = 0.762). Conclusions: We report the real-world outcomes of two chemotherapeutic regimens used in consecutive patients with advanced carcinoma penis. Both PC and CF seemed effective and safe. However, approximately half of patients with advanced carcinoma penis do not receive the planned/indicated chemotherapy. We need further prospective trials regarding the sequencing, protocols and indications of chemotherapy in this malignancy.

Multifocal intraosseous pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma: A rare presentation of an uncommon tumor.

ABSTRACT: Pseudomyogenic hemangioendothelioma (PHE) is an uncommon mesenchymal neoplasm of intermediate malignant potential showing endothelial differentiation. Around 20 cases of primary osseous PHE have been reported to date. A 16-year-old boy presented with complaints of pain in his right leg. Imaging revealed multifocal intramedullary and cortical-based lytic lesions involving long and small bones. Microscopic examination revealed plump, spindled cells arranged in fascicles and admixed "epithelioid" and "rhabdoid" cells sans vasoformative areas. By immunohistochemistry, the lesional cells were reactive for AE1/AE3, CD31, Erg, Fli1, and SMA, while immunonegative for CD34, myogenin, and S100. Nuclear expression of the INI1/SMARCB1 protein was retained. PHE is a rare entity, more so as a primary osseous lesion; therefore, awareness of the presence of this entity in the bone is the key to making a diagnosis. We discuss its clinicopathological features, differential diagnosis, and an attempt a short review of the literature.

PENS approach for breaking bad news in the oncology outpatient setting: a real-world report.

PURPOSE: Breaking bad news (BBN) is a vital part of oncology practice. We conducted this study to assess an abbreviated PENS protocol [Patient preference, Explanation, Next appointment, and Support] for BBN in oncology outpatient (OP) settings. METHODS: This observational study was conducted in a university teaching hospital, including cancer patients who were unaware of their condition and willing to discuss their disease status. The duration of BBN was the primary outcome. After the BBN session, patients filled a validated questionnaire; response scores of ≤ 13 were classified as content with BBN. RESULTS: Fifty patients (mean age 53.7 years, range 28-76) were included in the study. The average duration of BBN was 6.1 (range 2-11) min. Assessed by the response score sum, 43 (86%) patients were satisfied with BBN. Only three (6%) of the discontented patients felt that the BBN duration was too short. Most (94%) of patients reported that they understood the information imparted during the BBN session. After the session, 36 (72%) patients admitted to either feeling the same or reassured compared to before the session. The oncologists also were comfortable with PENS. CONCLUSIONS: The PENS approach is a practical method for BBN, especially when the oncologists have higher OP workloads. More extensive trials are required to validate the protocol in other settings. TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI/2021/07/034707).

Resource-appropriate selection of osteosarcoma treatment protocols in low- and middle-income countries.

Osteosarcoma is a rare malignancy; however, it is still the most common primary bone tumor in adolescents and young adults. Chemotherapy improves survival indubitably in osteosarcoma; nevertheless, the concern is the stagnant progress since the last several decades. There are a handful of active agents and unresolved issues, especially in choosing the ideal chemotherapy regimen. The oncology community is in equipoise regarding the position of high-dose methotrexate (HDMTX), mandatory or adjunct. The choice of therapy becomes widely relevant, including in low- and middle-income countries (LMIC), where HDMTX administration brings additional complexities. Research into novel non-HDMTX-based protocols adapted to the available resources is pivotal in improving disease outcomes, especially in LMIC. The current review focuses on real-world challenges in decision-making and provides a comprehensive overview of the evolution of treatment protocols in LMIC.

"PENS" approach for breaking bad news-a short and sweet way!

India has a distinct pattern of cancer care delivery, with unique sociocultural milieu and patient characteristics. In the current era of patient-centered and personalized care, there is an unmet need for an abbreviated protocol for breaking bad news to cancer patients suitable for the Indian outpatient setting. We propose a short four-step protocol for breaking bad news effectively and caringly, in the outpatient department of oncology clinics.

Recurrent cervical cancer treated with palliative chemotherapy: real-world outcome.

INTRODUCTION: Cervical cancer is the third most common cancer in India. There is limited data on the treatment of relapsed cervical cancer from India; therefore, we report the outcomes of patients with recurrent cervical cancer who were treated with palliative chemotherapy (CT). MATERIALS AND METHODS: This was a retrospective study of patients with recurrent cervical cancer who received palliative CT from January 2012 to December 2016. The demographic details, clinical profile and survival outcomes were collected. Patients were treated with carboplatin or paclitaxel and carboplatin. Local radiation was given for symptomatic patients. Patients were assessed for responses clinically and/or radiologically after three and six cycles of CT. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: Forty-six patients with recurrent cervical cancer were included in this analysis, with a median follow-up of 9.4 months. The median age was 49.5 (25-65) years and the median disease-free interval was 31.3 (2-196) months. Biopsy confirmation of relapse was established in 63%. The median number of CT cycles was six. Twenty-four (52.2%) patients completed six cycles of CT. The overall response rate was 56.5%. Patients with a complete or a partial response were more likely to have PFS > 6 months (p < 0.0001). Median PFS and OS were, respectively, 8.4 (95% CI 6.1-10.7) months and 10.3 (95% CI 6.8-13.8) months. The completion of all cycles of CT and the site of metastasis (nodal vs. visceral or combined) were found to be associated with OS. CONCLUSION: Palliative CT with paclitaxel carboplatin is a safe and effective option in Indian patients with recurrent cervical cancer, with more than half of the patients completing the prescribed CT. Further prospective trials may be required to place this treatment in the right context, in this era of immunotherapy and targeted therapy. However, knowing the outcomes in our population and prognostic factors will help in better prognostication of patients, thereby channelling our limited resources where necessary.

"Petite" p value: A Researchers' Dream! Readers, Beware of the Pit .

"What is the magic word for publication?" "The p value <0.05%" seems like an automatic answer from the researchers. Is that right? Let us take a quick peek at this seemingly simple gate-pass to publications! HOW TO CITE THIS ARTICLE: Mailankody S, Bajpai J, Gupta S. "Petite" p value: A Researchers' Dream! Readers, Beware of the Pit …. Indian J Crit Care Med 2020;24(Suppl 3):S140-S141.

Gender climate in Indian oncology: national survey report.

INTRODUCTION: There is evidence of under-representation of women in leadership roles and publications in oncology. However, there is little knowledge about their perceptions of professional environment, unique challenges and opportunities compared with male counterparts. The problem is more prominent in lower-income and middle-income countries like India and merits exploration. MATERIALS AND METHODS: A survey, 'Exploratory Study on the Challenges of Female Oncologists in India', was conducted among oncology professionals. We included questions on demography, working team details, role at work, perceived challenges for advancement of career, gender-related values brought into the team and the measures for improvement of gender disparity. Lead authorship data were collected from two Indian oncology journals. RESULTS: Of the 324 respondents, 198 (61.1%) were women. Majority of the respondents were medical oncologists (46.3%), ≤45 years old (69.4%) and working in universities and corporate hospitals (71.6%). One hundred eighty-nine (58.3%) respondents worked in teams with male majority, 50 (15.4%) in women-majority teams, while 85 (26.2%) worked in teams with gender equality. Of the 324 respondents, 218 (67.3%) had men managers, while 106 (32.7%) had women managers. Men led 160 (84.7%) male-majority teams; 45 (52.9%) gender-equal teams; and 13 (26%) female-majority teams (p<0.00001). Age >45 years was found to be associated with a leadership role (43% vs 25%, p=0.0012). The most significant barrier perceived for advancement of career for women was finding a work-life balance. Most respondents suggested provision of flexible training programmes to improve the disparity. Of the 558 journal publications inspected, 145 (26%) articles had a female first or corresponding author. CONCLUSIONS: The study brought out the current figures regarding gender climate in oncology practice and academia across India. We identified lead thrust areas and schemes to improve the gender bias. There needs to be action at international, national and personal levels to bring about an efficient gender-neutral workforce.

Outcomes of Oral Metronomic Therapy in Patients with Lymphomas.

Oral Metronomic chemotherapy (OMC) is used in patients with lymphoma who may not tolerate intravenous chemotherapy or have refractory disease. It is cheaper, less toxic and easy to administer. Adult patients with lymphoma who received OMC (combination of cyclophosphamide, etoposide and prednisolone) were included in this retrospective analysis. Response assessment was clinical with limited use of radiology. Progression free and overall survival (PFS and OS) were calculated from the time of start of OMC until documentation of disease progression or death. Between 2007 and 2017, 149 patients were given OMC [median age: 62 years (19-87); 94 patients (63.1%) male]. Majority [112 patients (75.2%)] had stage III/IV disease. The most common subtype of lymphoma was diffuse large B cell lymphoma (40.9%). OMC was used at diagnosis in 41 patients (27.5%) and after relapse in 108 patients (72.5%). Overall response rates were 43.9 and 41.7% with clinical CR in 14 (34.1%) and 21 (19.4%) in patients given first line and later lines of OMC respectively. After a median follow up of 12 months (range 1-123 months), median PFS and OS were 10.5 (95% CI 8.6-12.5) and 18.8 (95% CI 12.1-25.5) months respectively. PFS and OS at 12 months were 47.6 and 64.2% respectively. Though OMC is used in many centers in India, there is scanty published information on its efficacy in lymphoma. In this analysis, we demonstrate its activity in a subset of patients with predominantly high-grade and advanced stage NHL. OMC is a useful option in frail patients and a small proportion can achieve deep and long lasting responses.

Cerebrospinal fluid matrix metalloproteinase 9 levels, blood-brain barrier permeability, and treatment outcome in tuberculous meningitis.

OBJECTIVES: Tuberculous meningitis is characterized by elevated levels of matrix metalloproteinase 9 (MMP9) in the cerebrospinal fluid (CSF). However, it is unclear whether elevated MMP9 levels are associated with poor treatment outcome. We tested the hypothesis that pretreatment MMP9 levels in the CSF would be higher in tuberculous meningitis patients experiencing a poor treatment outcome. METHODS: We prospectively assessed the treatment outcome in a consecutive sample of human immunodeficiency virus-negative patients with tuberculous meningitis. We defined good outcome as survival without severe neurological disability (modified Rankin scale scores 0-2). We estimated levels of MMP9 and its tissue inhibitor (TIMP1) on pretreatment CSF samples. We used albumin index to assess blood-brain barrier permeability. RESULTS: We studied 40 patients (23 males [58%]) with tuberculous meningitis. Sixteen patients (40%) had stage 3 disease. On follow-up, 18 (45%) patients had a poor treatment outcome-15 patients died and 3 had severe neurological disability. Pretreatment MMP9 levels were not associated with treatment outcome (median [interquartile range], 254 [115-389] vs. 192 [60-383] ng/mL in good vs. poor outcome groups; P = 0.693). MMP9 levels did not correlate with the albumin index (Spearman's rho = 0.142; P = 0.381). However, MMP9 levels significantly correlated with CSF glucose levels (rho = -0.419; P = 0.007) and admission Glasgow coma scale score (rho = 0.324; P = 0.032). Likewise, TIMP1 levels also did not differ by treatment outcome (1239 [889-1511] vs. 1522 [934-1949] ng/mL; P = 0.201). MMP9/TIMP1 ratio that reflects net proteolytic activity was also not different between the two groups (0.191 [0.107-0.250] vs. 0.163 [0.067-0.34]; P = 0.625). CONCLUSION: Our findings do not support the hypothesis that pretreatment levels of MMP9 would be higher in tuberculous meningitis patients experiencing a poor treatment outcome. Further, MMP9 levels in the CSF did not correlate with blood-brain barrier permeability in patients with tuberculous meningitis.

Dengue Virus Infection Triggering Thrombotic Thrombocytopenic Purpura in Pregnancy.

We report a case of thrombotic thrombocytopenic purpura (TTP) that immediately followed symptomatic dengue virus infection in a pregnant lady. The patient developed dengue fever at 16 weeks of gestation, resulting in spontaneous abortion. Subsequently, fever reappeared with persistent thrombocytopenia and jaundice. Investigations revealed microangiopathic hemolysis; there was no evidence of disseminated intravascular coagulation. The TTP episode resolved after six cycles of therapeutic plasma exchange with fresh-frozen plasma. An ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif 13 repeats) activity assay, done during convalescence, showed normal activity. The patient had an uneventful second pregnancy and has remained free of TTP recurrence for more than 2 years now. We review the pathophysiological basis of TTP in dengue infection, and suggest that jaundice with disproportionate elevation of serum aspartate aminotransferase level in a patient with dengue should arouse the suspicion of TTP.