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.

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.

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.

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.

Synchronous primary cancers: Renal cell carcinoma and rectal cancer.

Although cancers of rectum and kidney are common malignancies, the occurrence of primary synchronous neoplasms of these organs has been reported rarely. Very few case reports are available in literature till date. The relationship between these two events remains unclear, probably because of the rarity of the association. In this report, we describe incidentally detected renal cell carcinoma in an elderly man, during staging workup of rectal adenocarcinoma and both malignancies were surgically managed simultaneously with curative intent.

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.

Metastatic thymic epithelial tumors: A regional cancer center experience.

BACKGROUND: Thymic epithelial tumors (TET) are the most common tumors of the anterior mediastinum. Patients with advanced/metastatic disease are usually treated with palliative chemotherapy (CT). Unfortunately, even though various palliative CT regimens have been used for long time, there is a real scarcity of published Indian data regarding the experience of palliative CT in metastatic TET (mTET). MATERIALS AND METHODS: This is a retrospective analysis of mTET patients treated between January 2010 and September 2017. Patients who received at least three cycles of first-line palliative CT were included for analysis of response rates, toxicity, and survival and prognostic factors. RESULTS: Of the 49 mTET patients, 27 (55.1%) were males. The median age at diagnosis was 52 years (range: 25-65). Eighteen patients (36.7%) had Masaoka Stage IVa disease, and the rest of the patients had IVb disease. The most common site of metastasis was pleuropericardium (n = 18), followed by lungs (n = 16) and lymph nodes (n = 9). The median progression-free survival and overall survival (OS) were 11.2 months (95% confidence interval [CI], 8.7-13.6) and 20.2 months (95% CI, 17.1-22.8), respectively, for the whole cohort (n = 49). The median OS of patients with Stage IVa disease was significantly better than that of the patients with Stage IVb disease (log-rank P = 0.000). Moreover, the "responders" to first-line CT had a significantly better median OS than the "nonresponders" (log-rank P = 0.000). Various first-line palliative CT regimens were well tolerated in our patients. CONCLUSION: Adriamycin Cisplatin Vincristine Cyclophosphamide (ADOC), Cyclophosphamide Adriamycin Cisplatin, and paclitaxel + carboplatin all are viable first-line palliative CT options for mTET and showed a comparable survival in Indian patients. The present study suggested that "responders" to first-line CT and those with Stage IVa disease might have a better survival than "nonresponders" and those with Stage IVb disease, respectively.

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.

Diffuse large B-cell lymphoma in elderly: Experience from a tertiary care oncology center in South India.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is the most frequent non-Hodgkins lymphoma in the elderly. With the rising proportion of older persons in India, it is important to study current patterns and management of this disease, given that data in this regard are scarce in Indian settings. The aim of this study was to document the clinical features of DLBCL among elderly patients and their outcome over 7 years at a tertiary care oncology center. MATERIALS AND METHODS: This was a retrospective records review of 119 DLBCL cases between January 2007 and January 2015 aged 60 years and above done at Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India. Clinical staging was done according to Ann Arbor staging as modified by Cotswold's and International Prognostic Index (IPI) calculated. RESULTS: The mean age was 69.54 years (±5.44) with male: female ratio of 1.52:1. B symptoms were seen in 33% of patients. Thirty-six percent of the patients had stage II disease. The advanced stage was seen in 12% and bulky disease in 9.5%. Bone marrow was involved in 12%. The most common extranodal site was the head and neck region. The distribution according to the IPI was as follows: Low risk 38 (31.93%), low-intermediate risk 53 (44.54%), high-intermediate risk 20 (16.80%), and high risk 8 (6.72%). Among 119 patients, 98 (64.7%) received treatment with either combination of rituximab, cyclophosphamide, adriamycin, vincristine, epirubicin, and prednisolone. Overall response rate was 63.26% with a complete response rate of 38.77%. The overall survival ranged from 2 to 123 months with the median being 9.5 months. CONCLUSION: In elderly, DLBCL is common in seventh decade and most of them present in an early stage and low IPI. The incorporation of rituximab to anthracycline based chemotherapy shows a significant improvement in survival in elderly DLBCL.