Clinical Profile and Outcome of Adult Classical Hodgkin's Lymphoma: Real World Single Centre Experience.

Hodgkin's lymphoma treatment outcomes have been the true success story of modern medicine. Various data from western as well as Indian studies are available for classical Hodgkin's lymphoma (cHL). Here we report treatment outcomes from a tertiary cancer care centre in Karnataka over a 5 year period. This was a retrospective review of cHL cases aged 15 years and above diagnosed between January 2015 and December 2019 at Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India. The case files of the patients were retrieved and relevant data was collected. Two hundred patients of cHL were included in this study. Median age was 28 years with male to female ratio of 1.56:1. B symptoms were present in 58% cases. Mixed cellularity (46.5%) was the most common histological subtype. Majority patients had advanced stage at presentation (stage III/IV) (62.5%). Extranodal disease was present in 19.5% cases. GHSG early-favourable cases were 15.5%, early-unfavourable cases were 22.0%, while 62.5% were advanced cases. The most common chemotherapy regimen used was ABVD. Eighty-three (41.5%) patients received radiation therapy. Median follow-up was 34.2 months (range 4.1-67.8). The rates for complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) were 84.5%, 8.5%, 5.0% and 2.0% respectively. PFS and OS rate at 6 years were 69.5% and 84.1% respectively. HL is one of the malignancies with high cure rate. The treatment outcome at our centre is comparable to western data and data from other tertiary centres from India.

Study of Biomarker Discordance between Primary and Recurrent Sites and its Clinical Implications in Metastatic Breast Cancer : A Single Institutional Study from India.

S. Shanthala Immunophenotypic discordance of receptors between primary and metastatic sites significantly impacts treatment outcomes. Current international guidelines recommend rebiopsy of accessible metastatic lesions to reassess tissue biomarkers. While existing literature on biomarker changes is conflicting and heterogeneous, similar studies on the Indian cohort of breast cancer patients are lacking. In this context, we aimed to evaluate the frequencies of biomarker changes between biopsies from primary and recurrent sites, and their association with various clinicopathological characteristics, including the type of metastasis and treatment in metastatic breast cancer (MBC) patients. This is an ambispective study performed at a single center. Immunohistochemical (IHC) expression of paired primary and recurrence samples of MBC patients was reviewed for the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2), and Ki-67. Concordance, loss, and gain of receptors were assessed based on the Allred scores for ER, PR, and HER2. Ki-67 was assessed based on a 14% cutoff. Further, receptor changes were studied in relation to age, menopausal status, morphology, grade, stage, metastatic sites, interval between biopsies, and treatment. At progression, biopsies were obtained from 41.18% of locoregional recurrence and 58.82% of metastatic sites. Despite high discordance of 47% for ER and 68.6% for PR, true receptor conversion was observed in 9.8%, 21.56%, and 5.88% for ER, PR, and HER2, respectively. There was a significant correlation between age and ER discordance ( p = 0.029). Loss in PR significantly correlated with a gain in Ki-67. Of all the metastatic sites, the lung was significantly associated with PR and Ki-67 concordance ( p = 0.008 and p = 0.0425, respectively). Discordance of receptors was neither related to the sites of biopsy (local recurrence or metastatic site) nor to the time interval between biopsies, prior chemotherapy, or hormone therapy. In conclusion, metastatic progression of the disease is accompanied by age-dependent discordance of ER. Unparalleled changes in PR in relation to ER suggest that ER-independent pathways may influence PR expression in MBC. Furthermore, the concurrence of PR loss with Ki-67 gain indicates an aggressive phenotype with disease progression. Hence, follow-up testing of samples for receptor expression is beneficial in determining prognosis and guiding therapeutic decisions.

Frequency of Programmed Death Receptor Ligand 1 Expression and Clinicopathological Factors Associated With Metastatic Triple-Negative Breast Cancer at a Tertiary Cancer Care Centre in South India.

Purpose Triple-negative breast cancer (TNBC) has a poor outcome compared to other subtypes. Immune checkpoint inhibitors (ICIs) have changed the treatment paradigm in metastatic diseases as well as in neoadjuvant setting. The response to these agents is affected by programmed death ligand 1 (PDL1) receptor expression which are reported objectively as a score. PDL1 is a prognostic marker also. Here, we present clinicopathological characteristics of metastatic TNBCs, report the proportion of PDL1 expression and its association with clinicopathological factors as well as survival. Methods This is a prospective study carried out at a tertiary cancer care centre in South India. Case records of all breast cancer patients treated in two years between August 2021 and July 2023 were reviewed, patients with metastatic TNBC were selected. Patient's characteristics, histological features, molecular profile, and treatment were analyzed. PDL1 testing was carried out on pretreatment tumor tissue sections with immunohistochemistry (IHC) (Dako 22C3). PDL1 staining was interpreted as negative or positive based on combined positive score (CPS), with an expression less than 10 considered negative. Results A total of 118 patients were analyzed. With a median age of 46 years (36-65 years), 52.5% (62/118) were premenopausal. Family history of Ca Breast was seen in 22% (26/118) patients. A majority of patients had left-sided tumor 55.9% (66/118). Visceral metastasis was more common 96.6% (82/118) than skeletal. Radical intent of treatment was adopted in 10% as patients had oligometastatic disease at presentation. As front-line treatment, anthracycline-based chemotherapy was administered to the majority 54.2% (64/118). The PDL1 expression with CPS more or equal to 10 was seen in 32.2% (38/118) patients. Survival was associated with menopausal status (p value=0.000) and family history (p value=0.028) but not with PDL1 nor sidedness in our study. Estimated survival at 12 months in PDL1 negative case is 10 ± 0.29 months, while in PDL1 positive case it is slightly more at 10 ± 0.75 months, but difference was not found to be statistically significant (p value=0.15). Conclusion TNBCs are highly aggressive subtype with limited treatment options and poorer outcomes. Our study shows PDL1 expression in 31.66% of the cases similar to other literature from India. Survival is associated with menopausal status and family history. No association was found between survival and PDL1 as well sidedness in our study.

Mortality Audit of Cancer Patients in the Department of Medical Oncology at a Tertiary Cancer Care Centre in South India.

Considerable advances in the diagnosis and treatment of cancer have made a huge impact on morbidity and mortality from neoplastic diseases. However, cancer remains the leading cause of death across the world. This is a retrospective study carried out at a tertiary cancer care centre (Kidwai Memorial Institute of Oncology, Bangalore) in South India. Case records of all cancer patients who died while receiving inpatient treatment between January 2022 and December 2022 under the Department of Medical Oncology were reviewed and studied. There was a total of 240 deaths. Out of these, the majority of deaths 147 (61.25%) were patients with haematological malignancies while the remaining 93 (38.75%) were patients with solid tumours. In patients with solid tumours, the majority 49 (52.7%) were in the age group of 40 to 60 years while only 18 (19.35%) patients were less than 40 years. The majority of patients were male sex i.e. 55(59.1%) and undergoing treatment with palliative intent 81 (87%). The most common organ was the lung in 21 patients (22.6%) followed by the breast while the most common system involved was the gastrointestinal tract in 28 (30.1%) patients. The most frequent cause of death was progressive disease in 72 (77.4%) while sepsis (11 patients; 11.8%) was the second most frequent cause of death in solid tumours. In haematological malignancies, also a significant number of 57 (38.8%) patients were in the age group of 40 to 60 years. Fifty-two (35.3%) patients were in the age group of 22 to 40 years. The majority were male sex (79 patients; 53.7%). About the phase of treatment, the majority of deaths 45 (30.6%) were during induction and under evaluation. Those with relapse/refractory disease were 38 (25.9%). A substantial number of patients had acute myeloid leukaemia 47 (32%) and five (3.4%) deaths were acute promyelocytic leukaemia patients. Twenty-three patients (15.6%) had acute lymphoblastic leukaemia. The most common cause of death was sepsis in 76 patients (51.7%) while intracranial bleeding was in 34 patients (23.1%). In some patients, there were multiple causes leading to death. Mortality audits are important to evaluate the services being provided at any centre. One can appreciate the lacunae in handling a particular disease or flaws in a treatment protocol or the staff delivering the treatment. Sepsis is the leading cause of death in patients with haematological malignancy; even in solid malignancy sepsis accounts for a substantial proportion of deaths and should be handled aggressively to save lives.

BRCA1 expression, its correlation with clinicopathological features, and response to neoadjuvant chemotherapy in high-grade serous ovarian cancer.

AIM: In high-grade serous ovarian cancers (HG-SOC), BRCA1 mutation is one of the predominant mutations reported by various studies. However, the non-mutational mechanisms of BRCA pathway inactivation in HG-SOC are unclear. We evaluated BRCA1 inactivation by estimating its expression with its repressor, ID4, in primary and neoadjuvant chemotherapy (NACT)-treated HG-SOC tumors with known therapeutic responses. METHODS: We evaluated the expression pattern of BRCA1 protein by immunohistochemistry in 119 cases of HG-SOC from a hospital cohort consisting of primary (N = 69) and NACT-treated (N = 50) tumors. Histological patterns (SET), stromal infiltration by lymphocytes (sTILs), and chemotherapy response score (CRS) were estimated by microscopic examination. Gene expression levels of BRCA1, and its repressor ID4, were estimated by qPCR. The association of BRCA1 protein and mRNA with clinicopathological features was studied. The relevance of the BRCA1/ID4 ratio was evaluated in tumors with different CRS. RESULTS: BRCA1 protein expression was observed in 12% of primary and 19% of NACT-treated HG-SOC tumors. We observed moderate concordance between BRCA1 protein and mRNA expression (AUC = 0.677). High BRCA1 mRNA expression was significantly associated with a more frequent SET pattern (p = 0.024), higher sTILs density (p = 0.042), and increased mitosis (p = 0.028). BRCA1-negative tumors showed higher expression of ID4 though not statistically significant. A higher BRCA1/ID4 ratio was associated with high sTILs density in primary (p = 0.042) and NACT-treated tumors (p = 0.040). CONCLUSION: Our findings show the utility of the BRCA1/ID4 ratio in predicting neoadjuvant therapy response, which needs further evaluation in larger cohorts with long-term outcomes.

Extranodal natural-killer/T-cell lymphoma, nasal type: An immunomorphological study from a regional cancer institute in India.

Introduction: Extranodal natural-killer/T-cell lymphoma, nasal type (ENKTL), is a rare, aggressive, predominantly extranodal non-Hodgkin lymphoma (NHL) of putative natural-killer (NK) cell and rarely T-cell origin, always associated with Epstein-Barr virus (EBV) infection and characterized by highly distinctive histopathological features with predilection for the upper aerodigestive tract. While the nasal cavity is the prototypical site, less frequently extranasal ENKTL can also occur. The objective of this case series is to study the immunomorphological features of ENKTL from a tertiary cancer centre as the data are sparse from India despite it being a distinct entity with characteristic clinicopathological features. Methods: We identified 11 cases of ENKTL from the departmental archives between January 2015 and June 2018. The clinicopathological and immunohistochemistry (IHC) findings of these tumors were analyzed. EBV encoded RNA (EBER) in situ hybridization (EBER-ISH) for EBV was done in eight cases. Results: The disease was more common in males (male: female ratio 1.8:1) with the mean age of 45 years (range 31-65 years). Sinonasal region was the most common site with 9 cases and skin and penis were involved in one case each. The patient with penile involvement on further investigations was found to have occult nasal involvement, Histomorphological features such as angiocentricity/angioinvasion was seen in seven cases (63.6%) and significant necrosis was present in all 11 cases (100%). All cases were uniformly positive for cytoplasmic CD3 and CD56 with high Ki67 proliferating index and EBER-ISH test for EBV was positive in all the eight cases. Conclusion: ENKTL is an aggressive NHL and should be differentiated from other T- and B-cell lymphomas as the prognosis and therapy differ. Nasal biopsies showing predominant necrosis and atypical lymphoid cells with angiocentricity must raise the suspicion of ENKTL and should be confirmed by immunomorphological and molecular studies.

Pre-phase strategy to mitigate first cycle effect in diffuse large B cell lymphoma.

CONTEXT: Treatment-related toxicities in DLBCL (diffuse large B cell lymphoma) patients are higher in the initial phase of treatment (first cycle effect). Implementation of pre-phase treatment before definitive chemotherapy had been shown to alleviate some of these side-effects in a non-randomized study conducted earlier in our institute (Lakshmaiah et. al., Eur J Haematol 100:644-8, 2018). AIMS: This study was aimed at validating the role of pre-phase treatment in newly diagnosed DLBCL patients. SETTINGS AND DESIGN: All newly diagnosed patients with DLBCL above the age of 18 years were evaluated for eligibility and prospectively enrolled. A single-arm prospective study was conducted at the Department of Medical Oncology, in our institute from July 2015 to December 2019. METHODS AND MATERIAL: Patients received vincristine and prednisolone as pre-phase treatment for 7 days after which definitive chemotherapy was instituted on day 1. They were followed up for 30 days post-first cycle chemotherapy. STATISTICAL ANALYSIS USED: Paired Student's t tests and Wilcoxon signed-ranks test were used for comparison of various clinical variables as appropriate. P value of less than 0.05 was considered significant. RESULTS: Among the 180 patients who were included in study, performance status improvement was noted in significant number of patients (p < 0.001). 38.4% achieved an ECOG (Eastern Cooperative Oncology Group) performance status of 0 post-pre-phase therapy. Febrile neutropenia was observed in 12.8% in the present cohort as compared to the historical non-pre-phase cohort (34%). CONCLUSIONS: Pre-phase therapy significantly improves the performance status and diminishes neutropenia rates in DLBCL patients.

Comparison Between CHOP and DAEPOCH with or Without Rituximab in Adult High Grade B Cell Lymphoma, Not Otherwise Specified; A Retrospective Study From a Tertiary Cancer Hospital in South India.

Lymphoma that on morphology appear blastoid or intermediate between DLBCL and BL but who lack myc and bcl-2 and/or bcl-6 rearrangements are grouped under high grade B-cell lymphoma, not otherwise specified (HGBL, NOS). Only a few studies have yet compared the outcome of HGBL, NOS treated with different chemo-immunotherapy regimens. HGBL, NOS patients were analyzed retrospectively, who were treated with CHOP or DAEPOCH regimens every 21 days for six cycles with or without rituximab. The primary clinical objective was progression free survival. One and two year PFS rates were 29.4% and 20.6% for the CHOP arm and, 65.2% and 47.8% for the DAEPOCH arm respectively. There was statistically significant difference in mean PFS between the arms (DAEPOCH vs CHOP: 19.7 months vs 12.8 months; HR = 0.44, p = 0.02, 95% CI: 0.22-0.88). One and two year OS rates were 91.1% and 20.5% for the CHOP arm and 95.6% and 60.8% for the DAEPOCH arm respectively. Mean OS was significantly better for DAEPOCH arm (28.1 months vs 20.7 months: HR = 0.43, p = 0.03, 95% CI: 0.20-0.92). Grade 3 and 4 hematological and non-hematological toxicities were more common in DAEPOCH arm. There were 2 treatment related deaths, 1 in each arm (4.3% for DAEPOCH vs 2.9% for CHOP). HGBL, NOS is a heterogeneous group of aggressive lymphoma associated with early relapse in nearly half of the cases. Intensive regimens like DAEPOCH is associated with improved outcome in terms of PFS and OS. Though toxicities are more with DAEPOCH, they are manageable and treatment related mortality is low.

Discordance in clinical versus pathological staging in breast cancer: Are we undermining the significance of accurate preoperative staging in the present era?

BACKGROUND: The present era of individualized treatment for breast cancer is influenced by the initial disease status including the anatomical extent, grade, and receptor status. An accurate preoperative staging is the basis of treatment planning and prognostication. Our study aims to determine the discordance between the preoperative clinical and the postoperative pathological stages of breast cancer patients. METHODOLOGY: The medical records of all non-metastatic breast cancer patients from January 2017 to December 2018 who underwent upfront surgery were reviewed. They were staged as per the eighth AJCC and the concordance between the clinical (c) and pathological T (tumor), N (nodal), and final AJCC stage was studied. A Chi-square test was used to determine factors that significantly correlate with disease discordance. RESULTS: A total of 307 breast cancer patients were analyzed. Among these, 43.3% were hormone receptor-positive, 30.6% were Her2 positive and 26% were triple-negative. Overall stage discordance was seen in 48.5% (n = 149) patients (upstaging in 22.1%, downstaging in 26.4%). The discordance rate was 48.9% for T stage (cT versus pT) and 57.4% for N stage (cN versus pN). Among patients with clinically node-negative disease, 53.4% were found to have positive nodes on histopathology, while 27.2% had vice versa. Overall, the factors associated with upstaging were ER-positive, Her2 positive and triple-negative status (all p < 0.05), while none of the factors showed significant association with downstaging. CONCLUSIONS: About half of breast cancer patients had discordance between clinical and pathological staging with higher discordance in the nodal stage. This changes the disease prognosis, and may also affect the offered surgical treatment and radiotherapy. Thus highlighting the need for a precise pre-operative staging. Also, this information will aid clinicians in discussions with patients, keeping in mind the likelihood of change in disease staging and management.

Rapidly Progressing Plasma Cell Leukemia with Underlying Plasmablastic Morphology: A Rare Case Report of a 25-Year Old Male.

Multiple myeloma constitutes a wide spectrum of diseases, ranging from slow-growing monoclonal gammopathy of undetermined significance to rapidly progressing plasma cell leukemia. It is a very rarely diagnosed hematological malignancy in those less than 30 years of age. A 25-year-old male presented with complaints of fatigue and low-grade fever. On investigation, he was found to have bicytopeina and features of tumor lysis syndrome. Initially, this was thought to be indicative of acute leukemia. However, upon further analysis with bone marrow biopsy, serum protein electrophoresis, and immunofixation, it was determined that the patient had an IgG myeloma with plasmablastic morphology. It rapidly progressed and the peripheral smear started showing clusters of plasma cells suggesting a picture of plasma cell leukemia. The patient succumbed to this aggressive disease despite treatment. This case illustrates that myeloma should also be included in the differential diagnosis for young patients, especially the rare plasmablastic variant, which can be misdiagnosed as acute leukemia. The aggressive morphology also tends to show rapid progression to plasma cell leukemia, which has a poor prognosis.

A Pilot Study on the Addition of Tramadol or Eutectic Mixture of Local Anesthetics (Prilocaine Plus Lignocaine) to Local Lignocaine Infiltration for Prevention of Bone Marrow Aspiration/Biopsy Associated Pain.

Objectives Bone marrow aspiration although being a common procedure is associated with significant pain and its reduction remains an unmet need. We evaluated the use of tramadol and eutectic mixture of local anesthetics (prilocaine plus lignocaine) (EMLA) for reducing the severity of pain. Materials and Methods In this pilot study, we compared the addition of either tramadol 50 mg per oral (T) or EMLA local application (E) or no intervention (L) in addition to the usual procedure of local infiltration with lignocaine 2% before bone marrow aspiration and biopsy (BMAB) in adults suspected/confirmed with malignancy. Both, tramadol and EMLA were administered 1 hour prior to the procedure. Primary end point was reduction in pain intensity with these interventions compared with local infiltration alone. Pain was assessed using numerical FACES pain scale, a visual analogue scale. Secondary end points were to see the effect on pre procedure apprehension and to find out the other factors associated with increased pain related to the procedure. Statistical Analysis and Results A total of 300 patients were included in the study, 100 each in tramadol (T), EMLA (E), and only lignocaine local infiltration (L) arms, respectively. The mean pain intensity on the visual scale was significantly lower in the tramadol arm (T, E, L-3.4, 4.4, 4.7, respectively) ( p < 0.0005). There was a significant reduction in percentage of patients who experienced moderate/severe pain (four or more) in the tramadol arm (T, E, L-45, 77, 82%, respectively) ( p < 0.0005). Duration of procedure >10 minutes, body mass index >30, ECOG (Eastern Oncology Group) performance status ≥3, and age >50 years were positively correlated with more pain. Leukemia patients experienced significantly more pain compared with patients with lymphoma and other solid malignancies. Tramadol was well tolerated. No significant effect on pre-procedure apprehension was noted in any of the arms. Conclusion Tramadol appears to have a preventive effect on bone marrow aspiration/biopsy-associated pain and appears to be well tolerated, whereas EMLA was not associated with such an effect. Larger studies may be done to ascertain the same.

Follicular Lymphoma in Young Adults: Study from a Regional Cancer Center in South India.

Objective Follicular lymphoma (FL) is a disease of the elderly. It is postulated that younger patients have distinct tumor biology and treatment outcomes. Various lymphoma groups across the world have studied this to understand if young adults (YAs) need a different treatment approach. Our study fills the void in data from an Asian country on YA population with FL. Patients and Methods We retrospectively analyzed young patients (age ≤40 years) diagnosed with FL at our center from 2012 to 2018. Their disease characteristics, treatment details, and outcomes were studied to examine any association between various parameters and survival. Results There were 28 young FL patients included in our study that constituted 14.6% of FL cases (males: 53.5% and females: 46.5%). The median age at diagnosis was 36.5 years. Most of the patients presented in an advanced stage, 57% had extranodal involvement, and 39.3% had bone marrow involvement at the time of presentation. The most common chemotherapy regimen used was cyclophosphamide, vincristine, and prednisone. Half of them received chemoimmunotherapy and only 18% continued rituximab as maintenance therapy. The overall response rate was 92.9% ( n = 26), and the remaining two patients had progressive disease while on treatment. The median progression free survival (PFS) was 6.1 years and median overall survival (OS) was not reached. On univariate analysis, extranodal disease was associated with a lower PFS ( p = 0.06) and low hemoglobin showed a significant association with OS ( p = 0.005). On multivariate analysis, none of the factors showed a significant association with survival. Conclusion Most YAs present with advanced disease with a good response to treatment and favorable outcomes.

Metastatic hormone receptor-positive breast cancer in CDK 4/6 era: An outcome audit.

BACKGROUND: The treatment landscape of metastatic hormone receptor (HR) positive breast cancer has been changed in recent years. Availability of CDK 4/6 inhibitor and other hormone therapy has changed the treatment algorithm for these patient, we retrospectively analyzed our metastatic HR positive breast cancer patients. MATERIALS AND METHODS: In this study, we retrospectively analyzed the case records of hr positive metastatic breast cancer patient treated at department of medical oncology from October 2016 to September 2018. Demographical characteristics, site of metastasis, objective response and clinical benefit response and toxicity profile were analyzed. RESULTS: We treated a total of 178 patients of MBC with HT at our center during the study period. One hundred fifty-two patients received HT alone (control group) and 26 patients received HT and CDK 4/6 inhibitor (study group). The median age of patients was 56 and 58 years in the control group and study group. The ORR was 41.7 versus 57.9 (95% CI [1.01-2.56]), and the CBR was 66.1% versus 78.9%; (CI [1.18-3.56]) (P < 0.05) of the patients in control and study groups, respectively. CONCLUSIONS: Among patients with HR-positive, advanced breast cancer, hormone therapy is efficacious addition of CDK 4/6 inhibitor improve the efficacy with tolerable side effects.

Primary mucinous carcinomas of the lung: Clinical characteristics and treatment outcomes.

INTRODUCTION: Invasive mucinous adenocarcinoma (IMA) of the lung is a distinct histologic variant of adenocarcinomas comprising about 2%-10% of lung adenocarcinomas. A large proportion of IMAs carry KRAS mutations and only rarely epidermal growth factor receptor (EGFR) mutations or ALK/ROS translocations; thus, most cases are not amenable for targeted therapy at present. This study was conducted to elicit the unique clinicopathological characteristics of IMA. MATERIALS AND METHODS: Medical records of patients diagnosed with IMA by needle biopsy at Kidwai Cancer Institute, Bangalore, from 2013 to 2018, were retrieved and reviewed. Statistical analysis was performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). RESULTS: Four hundred and ninety cases of needle biopsy of the lung were diagonosed at our institute between January 2013 and December 2018. Nine cases (1.8%) were diagnosed as IMA. The median age of presentation was 59 years. Six (66.7%) were current smokers with pack-year > 20. Three (33.3%) of the cases were initially misdiagnosed as pneumonia in view of computed tomography findings. The lung was the most common site of metastasis (77.8%). Serum Carcinoembryonic Antigen (CEA) was elevated in six cases (66.7%). None of the cases had any driver mutations in EGFR gene or ALK and ROS1 translocations. All cases were treated with pemetrexed-carboplatin doublet followed by pemetrexed maintenance till progression. The median progression-free survival (PFS) was 15 months (range: 5-18 months). Docetaxel was given as the second-line chemotherapy in all progressed patients. Best response noted was stable disease, seen in 4 (57.1%) cases. The median PFS for docetaxel was 6 months (range: 3-8 months). The median overall survival was 22 months (range: 9-27 months). Patients with initially raised CEA at progression had a serial rise in serum CEA. CONCLUSIONS: IMA is rarely diagnosed on needle biopsies due to insufficient tissue. They mimic pneumonia on imaging, thus delaying diagnosis. EGFR mutations, ALK, and ROS1 translocations are usually negative making them ineligible for tyrosine kinase inhibitors. Response to chemotherapy is modest.

Socioeconomic and administrative factors associated with treatment delay of esophageal and gastric carcinoma: Prospective study from a tertiary care centre in a developing country.

This study was aimed to analyze the spectrum of time intervals, from the onset of symptoms to the commencement of treatment in esophagogastric cancers. Factors influencing these time delays and correlation between these time points with variables including socioeconomic strata, educational level, histopathology, location of tumor and the initial modality of treatment were assessed. STUDY SETTING AND METHODS: A prospective analysis of patients with esophagogastric cancer presenting to a single tertiary care unit over a period of 12 months was performed. Histopathology other than adenocarcinoma and squamous cell were excluded. RESULTS: 202 patients were enrolled in the study. Most patients presented with advanced disease, i.e. 91.5 % of esophageal and 90 % of gastric malignancies belonged to either stage 3 or stage 4 as per American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system. The median delay from the appearance of the first symptoms to initiation of treatment was 15 weeks (range 4-64). Patient related factors contributed to a significant delay [median of 5 weeks (range 1-24)]. Administrative factors were responsible for median delay of 3 weeks (range 0.5-20). Curative multimodality treatment was administered in 62.5 % of patients. Significant longer delay was influenced by socioeconomic strata, educational level, evaluation by non-specialist (p < 0.05). No relationship was noted between histopathology, location of tumor or initial modality of treatment. CONCLUSIONS: Delays in our setting is much more than that is seen in Western and even some Asian countries. An important component of delay is administrative related factors. These may be intervened at the hospital level compared to other factors which may need long term community oriented approaches.

Follicular lymphoma transforming to DLBCL and reverting back to follicular lymphoma at relapse-a case report.

BACKGROUND: Transformation of low-grade follicular lymphoma to high-grade diffuse large B cell lymphoma (DLBCL) is known. However, the opposite is not commonly reported. In this report, we present a case of follicular lymphoma that underwent transformation to DLBCL. Three years after treatment for histologic transformation, the patient presented again with low-grade follicular lymphoma at the same site which is unusual in the natural history of follicular lymphoma. CASE PRESENTATION: A 50-year-old female patient presented to us with complaints of slowly progressing swelling in the neck on the left side for a duration of 1 year. Past history of the patient revealed a diagnosis of follicular lymphoma in 2004 for which the patient had taken prednisolone and chlorambucil. Details of staging were not available with the patient. After a complete work-up, she was diagnosed as DLBCL, stage IIIE. She was treated with 6 cycles of CHOP regimen. She had very good response to chemotherapy. However, she defaulted and was lost to follow-up. She presented again after 3 years with history of painless progressive swelling in the right side of the neck for the last 1 year. Examination revealed cervical lymph nodes and ascites. This time, a repeat biopsy and immunohistochemistry was suggestive of follicular lymphoma. In view of significant ascites, she was started on chemotherapy with CVP regimen. After 6 cycles, she has good partial response and resolution of ascites. She is currently on follow-up. CONCLUSIONS: We have presented a case of FL that has transformed to DLBCL after 10 years of diagnosis. After HT, she was treated with CHOP chemotherapy and the patient relapsed again after 3 years with follicular lymphoma histology. This case highlights the unique and varied natural history of follicular lymphoma that may be attributed to different subclones of malignant cells that may have arisen from a common progenitor FL cell and differential effect of chemotherapy on these subclones.

CML in Elderly: Does Age Matter?

The median age of diagnosis for chronic myeloid leukemia (CML) in India is 35 years on the contrary to western literature which is 47 years. The outcome of the elderly patient in CML TKI era is not reported from the Indian population. However, Western literature suggests that use of TKI alleviate the adverse impact of age in outcomes of CML. This study was carried out to analyze the clinical profile and outcome of elderly, in comparison with younger patients with CML. We retrospectively analyzed CML patients treated at our department from January 2008 to December 2017. The data cutoff date was December 2018. The cohorts of 712 patients were divided into two groups. Patients belonging to the age group of ≥ 60 years were classified as the study group and those who were 18-60 years were used as controls. Patient's clinical history, examination and milestones in terms of achieving hematological, molecular responses and toxicity profile were also recorded. The total of 712 patients, 52 patients in the study group and 660 patients in the control group were treated during the study period. The study group was having more co-morbidities than the control group (15.3% vs. 4.5%). Patients having high-risk EUTOS score were similar in both groups (38.4% vs. 37.6%). The patients presented in blast phase were higher in the study group as compared to control group (9.6% vs. 6.36%) but the differences were not statistically significant. Rates of achieving a hematological response at 3 months (85.1% vs. 86.89%) and the major molecular response at 18 months (54.3% vs. 60.16%) were almost similar in both groups. However, hematological toxicity, muscle cramps and gastritis were reported more in elderly patients. The outcome of CML patients in TKI era do not differ in elderly patients. However, toxicity profile was not significantly inferior in elderly patients.

Detection of clinically relevant epidermal growth factor receptor pathway mutations in circulating cell-free tumor DNA using next generation sequencing in squamous cell carcinoma lung.

BACKGROUND: Limited repertoires of targets are available in the management of squamous cell carcinoma lung. In this study, we analyzed epidermal growth factor receptor (EGFR), RAS, BRAF mutations in lung cancer patients of squamous cell histology using next-generation sequencing (NGS) on the circulating cell-free DNA (cf-DNA). MATERIALS AND METHODS: In this prospective observational study, patients with squamous cell carcinoma lung, either newly diagnosed or having a progressive disease on prior therapy were eligible. Cf-DNA was extracted from peripheral blood and analyzed for EGFR, KRAS, NRAS, and BRAF mutations using NGS. RESULTS: Sixteen patients were enrolled over a period of 1 month. The mean cf-DNA quantity extracted from the plasma was 96.5 ng (range, 15-200 ng). Eight clinically relevant mutations in the EGFR pathway were identified. These include Exon 21 mutations in 4 patients, Exon 20 mutation in onepatient, complex mutations with coexisting Exon 21 and Exon18 in one patient and KRAS Exon 2 mutations in two patients. CONCLUSION: cf-DNA is a minimally invasive technique for detection of clinically relevant mutations in lung cancer patients. The use of novel advanced techniques such as NGS may help in detecting EGFR pathway mutations in patients with squamous cell carcinoma lung.

Pro-oncogenic, intra host viral quasispecies in Diffuse large B cell lymphoma patients with occult Hepatitis B Virus infection.

Non Hodgkin lymphoma, predominantly Diffuse Large B-cell Lymphoma (DLBCL) has been reported to have a significant association with Hepatitis B virus (HBV). We investigated the presence of different gene segments of HBV in plasma, B-cells and tumor tissues from DLBCL patients and explored the genetic variability of HBV within and across different compartments in a host using Next Generation Sequencing. Despite all 40 patients being HBV seronegative, 68% showed evidence of occult HBV. Sequencing of these gene segments revealed inter-compartment viral variants in 26% of them, each with at least one non-synonymous mutation. Between compartments, core gene variants revealed Arg94Leu, Glu86Arg and Ser41Thr while X gene variants revealed Phe73Val, Ala44Val, Ser146Ala and Ser147Pro. In tumor compartments per se, several mis-sense mutations were detected, notably the classic T1762A/A1764G mutation in the basal core promoter. In addition, a virus surface antigen mis-sense mutation resulting in M125T was detected in all the samples and could account for surface antigen negativity and occult HBV status. It would be interesting to further explore if a temporal accumulation of viral variants within a favored niche, like patients' lymphocytes, could bestow survival advantage to the virus, and if certain pro-oncogenic HBV variants could drive lymphomagenesis in DLBCL.

TSC1/2 mutations as markers of response to everolimus in metastatic renal cell carcinoma: A case study.

We report a case of a 67-year-old man with pazopanib-resistant metastatic renal cell carcinoma (mRCC) who showed an exceptional response to everolimus. Furthermore, this patient had TSC1 and TSC2 mutations. Only a subset of patients with mRCC respond to mTOR inhibitors and emerging evidences indicate that TSC1 and TSC2 mutations could be markers of response to mTOR inhibition. The current case study supports these accruing evidences.