Role of prephase treatment prior to definitive chemotherapy in patients with diffuse large B-cell lymphoma.

BACKGROUND: During the treatment of diffuse large B-cell lymphoma (DLBCL) patients, treatment-related toxicities are higher in the initial phase of treatment (First cycle effect). Toxicities can be tumor lysis syndrome, deterioration in performance status, febrile neutropenia, and rarely mortality. Prephase treatment before definitive chemotherapy is used in European countries to alleviate these toxicities. METHODS: This was a non-randomized study carried out with the aim to evaluate the role of prephase treatment given prior to definitive chemotherapy in newly diagnosed DLBCL patients. Patients were divided into 2 cohorts "prephase cohort" and "non-prephase cohort." Prephase cohort received prephase treatment consisting of vincristine (1 mg) on -6th day and prednisolone 100 mg daily for 7 days (-6th day to day 0). Prephase treatment was followed by CHOP/R-CHOP chemotherapy on day 1. Non-prephase cohort received chemotherapy without prephase. Both groups were followed up for 30 days post-first cycle chemotherapy. RESULTS: A total of 100 patients with DLBCL (50 in each cohort) were enrolled. There was a significant improvement in performance status of the patients who received prephase. A majority of 92% patients attained ECOG performance status of either 0 or 1 before starting chemotherapy in the prephase cohort. Febrile neutropenia was lower (16%) in the prephase cohort as compared with the non-prephase cohort (34%; P = .037). CONCLUSION: Prephase treatment prior to definitive chemotherapy (CHOP ± Rituximab) improves the performance status and decreases first cycle effect in DLBCL patients.

Circulating Tumor Cell cluster phenotype allows monitoring response to treatment and predicts survival.

Circulating tumor cells (CTCs) are putative markers of tumor prognosis and may serve to evaluate patient's response to chemotherapy. CTCs are often detected as single cells but infrequently as clusters and are indicative of worse prognosis. In this study, we developed a short-term culture of nucleated blood cells which was applied to blood samples from breast, lung, esophageal and bladder cancer patients. Clusters of different degrees of compactness, classified as very tight, tight and loose were observed across various cancer types. These clusters show variable expression of cytokeratins. Cluster formation from blood samples obtained during the course of chemotherapy was found to be associated with disease progression and shorter overall survival. The short-term cultures offer a robust and highly reliable method for early prediction of treatment response in different cancer types.

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.

Every distant deposit is not a metastasis: Synchronous primaries do exist.

BACKGROUND: Synchronous occurrence of two malignant tumors is a rare event. With increasing use of sophisticated imaging modalities for staging, synchronous multiple tumors are more commonly detected now. Assuming the second primary malignancy as metastasis will change the intent of treatment from curative to palliative, greater awareness among oncologists is of paramount importance. This study is an example where thorough clinical examination and proper judgment resulted in correct diagnosis and appropriate treatment. MATERIALS AND METHODS: This is a prospective descriptive study. Patients diagnosed with synchronous primary tumors from January 2016 to November 2017 at our center were reviewed. RESULTS: Ten cases of synchronous primary malignancies were detected during this period. A total of 20 primary tumors were diagnosed. Lung carcinoma and gastrointestinal malignancies were the most common (five patients each). The median age was 59.5 years. Seven patients were male. Second primary tumor was suspected in four patients during clinical examination, while in six patients it was suspected on imaging. Even in the presence of two primary tumors, three patients were treated with curative intent. CONCLUSION: Possibility of synchronous second primary malignancy should always be kept whenever a distant deposit is detected at an unusual site. Histopathological evaluation of the lesion before assuming a metastasis will lead to accurate diagnosis, staging, and appropriate treatment.

Primary cutaneous B-cell lymphoma: A single-center 5-year experience.

BACKGROUND: Skin is the second most common site for extranodal non-Hodgkin's lymphoma (NHL). Most primary cutaneous NHLs are of T-cell origin (70%). Primary cutaneous B-cell lymphoma (PCBCL) is a rare entity. MATERIALS AND METHODS: Patients diagnosed with PCBCL between January 2012 and July 2017 at our center were retrospectively analyzed. RESULTS: Eight patients of PCBCL were diagnosed. Three patients (37.5%) were males while 5 patients (62.5%) were females. The median age at diagnosis was 45 years (range, 18-60 years). Scalp was the most common site of involvement (50% of the patients). Diffuse large B-cell lymphoma (DLBCL) was the most common histology (63%), with leg-type DLBCL diagnosed in 1 patient. Two patients had primary cutaneous follicle center lymphoma, whereas the remaining 1 patient had precursor B-lymphoblastic lymphoma. All 5 DLBCL cases were treated with CHOP chemotherapy, and rituximab was given to 3 patients. Of the primary cutaneous follicle center lymphomas, 1 patient with stage II disease was treated with CHOP and is alive without recurrence for the past 5 years, whereas the other patient is on observation alone. The patient with precursor B-lymphoblastic lymphoma was started on MCP-841 protocol; however, the patient did not complete the treatment and died after 11 months. CONCLUSIONS: PCBCL is a heterogeneous group of diseases and dividing them into subtypes, based on morphology and immunophenotype, has therapeutic implications.

Clinical profile and treatment outcomes of metastatic neuroendocrine carcinoma: A single institution experience.

BACKGROUND: Neuroendocrine carcinoma (NEC) is a rare tumor arising from the diffuse neuroendocrine system. Most of these present in the advanced stage and palliative chemotherapy remains the only option. The prognosis remains poor with the standard chemotherapy regimen of platinum and etoposide (EP) providing modest survival benefit. METHODS: The study was done for 3 years at a tertiary cancer center in South India. Patients with a diagnosis of metastatic NEC were analyzed for clinical and pathological characteristics. The treatment outcomes and prognostic factors were evaluated using appropriate statistical test. RESULTS: A total of 114 patients of metastatic NEC satisfied the inclusion criteria and were analyzed. Gastrointestinal including hepatobiliary tract (33%) was the most common site of primary disease followed by lung (26%), genitourinary (15%), head and neck (14%), and unknown primary (9%). On analysis of pattern of metastasis, liver (65%) was the most common site followed by bone (54%) and lung (42%). The median overall survival was 11 months with a statistically significant difference between pulmonary and extrapulmonary disease (8 vs. 13 months; P = 0.003). Ki67% value was strongly associated with prognosis (hazard ratio 0.517, 95% confidence interval; 0.318-0.840, P = 0.008) whereas age, sex, and lactate dehydrogenase level did not show any relation with survival. CONCLUSION: The outcome of advanced NEC with standard chemotherapy remains poor. Larger studies with other therapeutic and novel agents are warranted to improve the treatment outcomes.

Primary breast angiosarcoma - a single institution experience from a tertiary cancer center in South India.

INTRODUCTION: Primary angiosarcoma of the breast is a rare entity with incidence of less than 0.05% of all malignant breast neoplasms. It occurs in young females without any associated risk factors. The tumor behaves aggressively and has a poor prognosis compared to invasive ductal carcinoma. METHOD: It was a retrospective observational study done at a tertiary cancer center from January 2012 to December 2016. The medical records of patients diagnosed with primary breast angiosarcoma were reviewed for the study. Clinicopathological profile, treatment, and the outcomes were analyzed. RESULTS: Four patients were diagnosed with primary breast angiosarcoma out of 2560 breast cancer patients seen over a period of 5 years. Two had metastatic disease at presentation. Among four patients, two underwent surgery of the primary tumor, whereas, all received chemotherapy either as adjuvant or palliative setting. One patient received adjuvant radiation therapy. Three patients received 2nd line and one received 3rd line chemotherapy on disease progression. After a median follow-up of 18 months one patient was surviving on 3rd line chemotherapy with trabectedin. Other three succumbed to disease after progression. CONCLUSION: Due to a small number of this malignancy randomized studies are difficult to perform and optimum treatment strategy still need to be defined.

Correlation of BMI with breast cancer subtype and tumour size.

BACKGROUND: Breast cancer is a heterogeneous disease which is divided broadly into luminal, HER2 and basal type based on molecular profiling. Increased body mass index (BMI) has been associated with the risk of developing breast cancer but the association based on molecular subtype remains conflicting. METHODS: This was an observational study carried out over a period of 2 years. Nonmetastatic breast cancer patients were evaluated for the tumour subtype based on surrogate markers (ER, PR and HER2). The BMI of these patients was correlated with the tumour subtype and size. RESULTS: We studied 476 patients with breast cancer with the median age of 46 years (range, 25-86) and 58% were premenopausal. The mean BMI of the cohort was 24.1, which was significantly higher in postmenopausal women (24.9 versus 23.6, p < 0.05). Overall, only 10% of patients were obese. The mean BMI in the luminal, HER2 and TNBC subtypes was 24.7, 22.4 and 23.9, respectively (p < 0.01). Also, the mean tumour size in luminal, HER2 and TNBC subtype was 4.02, 3.80 and 4.27 cm, respectively (p = 0.158). CONCLUSION: The average BMI was higher in patients with luminal subtype followed by TNBC and lowest for HER2 at the time of diagnosis. The mean tumour size was numerically higher for TNBC and lowest for HER2 subtype although the difference was not statistically significant. Larger studies may provide clarity of association between the BMI and tumour subtype.

Role of Taxanes in Triple-Negative Breast Cancer: A Study From Tertiary Cancer Center in South India.

BACKGROUND: Breast cancer is the most common female cancer seen globally. Triple-negative breast cancer (TNBC) is a special subtype without any obvious target and optimum treatment remains challenging. The aim was to study the clinical, pathological profile and treatment outcome of TNBC patients. METHODS: This was a retrospective observational study of TNBC patients diagnosed from January 2010 to June 2012 at a tertiary cancer center in South India. Patient's clinical and pathological characteristics were studied. The 5-year estimate of survival for non-metastatic TNBC was done using the Kaplan-Meier method. RESULTS: Out of 804 patients of breast cancer, 237 were diagnosed as TNBC. The median age was 45 years and 58% were premenopausal. The 5-year disease-free survival (DFS) and overall survival (OS) for non-metastatic TNBC patients were 59% and 74%, respectively. The addition of a taxane to anthracycline-based regimen did not show a significant difference in DFS (P = 0.885) as well as OS (P = 0.856). CONCLUSION: The role of adding taxanes to anthracycline-based chemotherapy in adjuvant setting for TNBC remains controversial and larger prospective studies are warranted.