Is Optimal Cytoreduction Post Neoadjuvant Chemotherapy the Only Prognostic Factor in Advanced Ovarian Cancer?

Pravesh Dhiman, DNB (Medical Oncology).Background Epithelial ovarian cancer (EOC) is one of the leading causes of cancer-related death in women. Approximately 70% of patients with EOC are diagnosed in advanced stage [The International Federation of Gynecology and Obstetrics(FIGO stage III and IV)] with an expected 5-year survival rate of 30%. Numerous studies have shown that survival with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is noninferior to primary debulking surgery followed by chemotherapy. Materials and Methods In this retroprospective observational study, 50 patients with advanced ovarian cancer, diagnosed from January 2012 to January 2015, were included and followed-up till January 2017. Correlation of NACT with patient profile, CA125 levels, clinicopathologic parameters, progression-free survival (PFS), and treatment response was studied. Statistical analysis was performed using log-rank test and Kaplan-Meir survival plots. Results The extent of cytoreduction significantly correlated with PFS. The PFS was maximum in patients who had optimal cytoreduction (19 months) and 10 months in patients with suboptimal cytoreduction with p -value < 0.05. The survival was not significantly correlated with other parameters such as age, stage, preoperative CA125 levels, and ascites. Conclusions The extent of cytoreduction following NACT in this study was associated with statistically significant PFS advantage in patients who were able to undergo optimal cytoreduction, but not significantly correlated to other factors such as age, stage, preoperative CA125 levels, and ascites. NACT followed by interval cytoreduction is an important modality affecting survival in advanced EOC. Further studies and longer follow-up are needed to demonstrate survival advantage over standard treatment.

Bavituximab plus paclitaxel and carboplatin for the treatment of advanced non-small-cell lung cancer.

OBJECTIVE: Bavituximab is a phosphatidylserine (PS)-targeting monoclonal antibody with immune-modulating and tumor-specific vascular targeting properties. Preclinical studies have shown activity against numerous solid tumors and at least an additive effect in combination with chemotherapy. This study evaluated bavituximab in combination with paclitaxel and carboplatin in patients with previously untreated, locally advanced or metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This phase II, open-label study (NCT00687817) was conducted in 49 patients with stage IIIB/IV NSCLC utilizing a Simon two-stage design. Patients were treated with up to six cycles of carboplatin area under the concentration-time curve (AUC) 5 plus paclitaxel 175 mg/m2 every 21 days with weekly bavituximab 3 mg/kg followed by bavituximab monotherapy until progression or unacceptable toxicity. RESULTS: The primary efficacy endpoint of overall response rate (ORR) was 40.8% (complete response [CR] 2.0%, partial response [PR] was 38.8%). Median progression-free survival (PFS) and overall survival (OS) were 6.0 and 12.4 months, respectively. Treatment-related adverse events (AEs) occurred in 40.8% of patients. The most common treatment-related AEs were anemia (10.2%), asthenia, vomiting, paresthesia, anorexia, and fatigue (6.1% each). One patient with a central, cavitating squamous tumor developed fatal hemoptysis and aspiration. CONCLUSION: Bavituximab in combination with paclitaxel-carboplatin as first-line therapy demonstrated a tolerable safety profile and potential efficacy in this single-arm phase II trial in patients with advanced local or metastatic NSCLC. Randomized trials with this regimen are in progress. CLINICALTRIALSGOV IDENTIFIER: NCT00687817.

Nimotuzumab provides survival benefit to patients with inoperable advanced squamous cell carcinoma of the head and neck: a randomized, open-label, phase IIb, 5-year study in Indian patients.

OBJECTIVE: Overexpression of epidermal growth factor receptor (EGFR) in many cancers makes it an attractive therapeutic target. This study evaluated the clinical utility of nimotuzumab, a monoclonal anti-EGFR antibody, used concurrently with radiotherapy (RT) and chemoradiotherapy (CRT) in squamous cell carcinoma of the head and neck (SCCHN). METHODS: This open-label study randomized 92 treatment-naïve patients (1:1) with advanced SCCHN into chemoradiation (CRT ± nimotuzumab) or radiation (RT ± nimotuzumab) group by investigator's discretion; these were further randomized into CRT + nimotuzumab or CRT and RT + nimotuzumab or RT groups, respectively. Treatment included 6 cycles each of cisplatin (50 mg/week), nimotuzumab (200 mg/week), and RT (total dose, 60-66 Gy). Response (tumor size reduction) was assessed at Month 6 post-treatment and survival, at Month 60. RESULTS: Forty and 36 patients in the chemoradiation and radiation groups, respectively (intent-to-treat population) were evaluated. Overall response at Month 6 post-treatment was 100% with CRT + nimotuzumab, 70% with CRT, 76% with RT + nimotuzumab, and 37% with RT. At Month 60, overall survival was 57% with CRT + nimotuzumab, 26% with CRT (P = 0.03), 39% with RT + nimotuzumab, and 26% with RT (P > 0.05). Median overall survival was not reached for CRT + nimotuzumab; it was 21.94 months for CRT (P = 0.0078), 14.36 months for RT + nimotuzumab, and 12.78 months for RT (P = 0.45). Risk of death was 64% lower with CRT + nimotuzumab than with CRT (95%CI: 0.37, 1.56), and 24% lower with RT + nimotuzumab than with RT (95%CI: 0.16, 0.79). Thus nimotuzumab was safe and well tolerated with few mild to moderate self-limiting adverse events. CONCLUSION: Concurrent use of nimotuzumab with CRT/RT is safe and provides long-term survival benefit.

Trends in oesophagus and Stomach cancer incidence in Bangalore, India.

BACKGROUND: During recent decades, an increase in the incidence of certain oesophago-gastric cancer has been reported in some countries and in India. This study sought to analyze oesophageal and gastric cancer incidence trends in Bangalore by sex and morphology for the period 1982-2007. PATIENTS AND METHODS: Oesophageal and gastric cancer cases were drawn from Bangalore population-based cancer registry locating in Kidwai memorial Institute of Oncology started in 1982 under national cancer Registry Programme funded by Indian Council of Medical Research. Time trends in sex- and age-standardized cancer incidence rates were analyzed by site and histology over the study period, using relative change. RESULTS: Age-standardised oesophageal cancer incidence rates increased in males, in females failed to register a significant trend over the study period. Overall, gastric cancer decreased from 9.81 and 5.48 rates per 100 000 person-years in 1982-86 to 9.45 and 5.25 in 2002-07, among men and women, respectively. Where as oesophageal adenocarcinomas increased sharply in both sex, among men, oesophageal squamous cell cancer rates increased steadily from the mid-1982s onwards a bit decline was observed from 1997, the same trend observed in females. The gastric cancer decreased over the study period. There was a marked decrease in the incidence of oesophago-gastric cancer presenting with unknown and unspecified morphology reported. KEYWORDS: adenocarcinoma, Oesophageal and stomach, incidence, age specific rate, age adjusted rate, population-based registry, trends.

Clinical outcome of adjuvant endocrine treatment according to Her-2/neu status in breast cancer.

BACKGROUND & OBJECTIVES: An association between over-expression of proto-oncogene Her-2/neu and resistance to tamoxifen in estrogen receptor (ER) positive, primary and metastatic breast cancer has been suggested. HR+/Her-2/neu+ patients have a poor response to endocrine therapy, making this group a matter of debate. The present study was carried out to examine whether Her-2/neu expression in breast cancer patients predicted tamoxifen effectiveness. METHODS: An enzyme-linked immunosorbent assay (ELISA) specific for the extracellular domain of the Her-2/neu oncoprotein product was used to detect serum Her-2/neu levels in 207 patients with histological confirmed breast cancer. Tissue Her-2 /neu expression was studied in 100 breast cancer patients by immunohistochemistry (IHC) and compared with serum Her-2/neu levels by ELISA. RESULTS: Among 207 histologically confirmed breast cancer patients, 53 were serum Her-2/neu positive. Patients who were treated with surgery, chemotherapy, and radiotherapy showed significantly (P<0.05) reduced serum Her-2/neu levels, showing good response to treatment. Patients who were treated with tamoxifen in addition to the above regimen did not show any significant reduction in serum Her-2/neu levels showing resistance to treatment. INTERPRETATION & CONCLUSIONS: The present findings study support the hypothesis that Her-2/neu overexpression contributes to tamoxifen resistance. Trastuzumab or other growth factor inhibitors should be used in combination with tamoxifen, since monotherapy is not likely to be optimal in HR+/Her-2/neu+ tumours.

Risk scoring for predicting mucositis in Indian patients with esophageal carcinoma receiving concurrent chemoradiotherapy.

PURPOSE: Mucositis is a common and troublesome adverse effect of concurrent chemoradiotherapy, often causing treatment interruption and compromising treatment outcome. We sought to identify predictors of mucositis in southern Indian patients treated for gastroesophageal carcinoma. METHODS: Patients (N = 90) receiving cisplatin 40 mg/m(2) and concurrent local radiotherapy at 40 to 50 Gy for esophageal carcinoma were retrospectively assessed for predictors of mucositis. Hypothesized risk factors were age, presence of comorbid conditions, low white blood cell (WBC) count, nutritional status (assessed by serum albumin level), continuing tobacco use, elevated erythrocyte sedimentation rate (ESR) as a measure of acute inflammation, World Health Organization (WHO) performance status, and disease stage. Receiver operating characteristic (ROC) curves were drawn to identify cut-off values for risk factors, and a risk scoring model was developed. RESULTS: On the basis of cutoff values on ROC analysis, a risk score of 1 was assigned for each risk factor as follows: age > 50 years, ESR > 3 times upper limit of normal, albumin < 3.3 g/dL, WBC < 2.5 x10(9)/L, WHO performance status > 2, and > stage III disease, with use of tobacco and presence of any comorbid condition also each being assigned a score of 1. For individual patients, a score of < 3 was associated with a 25% risk of grade 3 or 4 mucositis, whereas a score of >/= 6 was associated with 80% risk. CONCLUSION: The scoring system is accurate in predicting the development of mucositis in southern Indian patients receiving concurrent chemoradiotherapy for esophageal carcinoma.

Bone metastasis in hepatocellular carcinoma: need for reappraisal of treatment.

Bone is an uncommon site of metastasis in patients with hepatocellular carcinoma (HCC), and often overlooked. We report two cases that had isolated bone metastasis; one of them had prolonged disease-free survival. The present series, along with the literature review, reinforces the idea that HCC should be considered in the differential diagnoses in patients presenting with metastases in bone. The presence of isolated bone metastases need not necessarily indicate poor prognosis, and all such patients need to be offered chemotherapy and at least one of the bone-directed therapies (either local radiation in cases of localized disease or bisphosphonates in the presence of extensive disease) as they may have a better outcome with therapy.

Irreversible sensorineural hearing loss due to Imatinib.

OBJECTIVE: We report probably the first case of bilateral irreversible sensorineural hearing loss caused by Imatinib. METHOD: A review of the world literature, concerning Imatinib toxicity is presented. RESULTS: We report a case of bilateral irreversible sensorineural hearing loss, in a 19-year-old male patient of chronic myeloid leukemia after 3 months of Imatinib therapy. Audiometric evaluation documented the findings. CONCLUSION: To the best of our knowledge, this is the first case report of Imatinib induced sensorineural hearing loss. This case indicates that treating oncologists should keep in mind that this drug too can produce ototoxicity.

Evaluation of immunohistochemistry and enzyme linked immunosorbent assay for HER-2/neu expression in breast carcinoma.

HER-2 is overexpressed in approximately 20-30% of invasive Breast Cancer. ECD of the HER-2 protein is frequently cleaved and released into the circulation, where it can be detected by ELISA in up to 45% of patients with metastatic breast cancer. The objective of our study was to compare the current methods for the detection of HER-2 protein. Tissue HER-2 levels were studied in 100 breast cancer patients by IHC and compared with serum HER-2 levels by ELISA. IHC frequency was 29%. Serum HER-2 ECD was positive in 42% of patients. A statistically significant correlation was observed. HER-2 detected by IHC correlates significantly with serum HER-2 levels detected by ELISA. Thus, ELISA is a reliable and economical tool to assess the HER-2 status in tumors, when breast tissue sample is not available.

Treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs. VIP) for poor-prognosis metastatic germ cell tumors.

BACKGROUND: In patients with small-volume disseminated disease of germ cell tumors, cure can be achieved with four cycles of bleomycin, etoposide, and cisplatin (BEP). However, around 20% of these cases are not curable. Strategies to improve cure rates have shown that none of the currently available modalities were superior to the others. Among the most used ones, BEP and VIP (etoposide, cisplatin, and ifosfamide) have been the most studied. However, there are no reports comparing the two, except for a few in abstract forms from southern India. Therefore, we did a treatment outcome and cost-effectiveness analysis of two chemotherapeutic regimens (BEP vs VIP) that are used in poor-prognosis metastatic germ cell tumors. MATERIALS AND METHODS: All male patients with germ cell tumors, diagnosed as having poor risk by IGCCCG, between January 2002 and December 2004 were included in the study. Clinical, laboratory, and other data were recorded. The patients were stratified into two categories on the basis of the type of chemotherapeutic regimen they received. RESULTS: In all, 46 patients were analyzed, with a median follow up of 26.6 months. The baseline characteristics (age, stage, PS, histology, and serum markers) were not different in the two treatment arms. There is no significant difference in the outcome with either of the chemotherapeutic modalities. VIP is less cost effective and more toxic compared to BEP. CONCLUSION: In view of the greater toxicity and cost of therapy, as well as lack of either overall or disease free survival advantage, VIP is not a preferred option for patients with high-risk germ cell tumors in the Indian setting and it is still advisable to treat patients with BEP.

Clinical utility of serum human epidermal receptor-2/neu detection in breast cancer patients.

BACKGROUND & OBJECTIVE: In breast cancer, the HER-2/neu gene is amplified in 20-30 per cent of cases. The mechanism by which the amplification/overexpression occurs is not known. Elevated serum HER-2/neu levels have been shown to be associated with a poor clinical prognosis and decreased survival in early stage breast cancer patients, and thus might help in management of the disease. The present study was therefore to estimate the serum HER-2/neu levels in breast cancer patients and associate with other prognostic factors. METHODS: Serum HER-2/neu levels were studied in 207 patients with cancer breast, 15 benign breast diseases (BBD) and 175 age-matched healthy controls. Patients' age, menopausal status, node and hormone receptor status were compared with serum HER-2/neu levels. RESULTS: Serum HER-2/neu overexpression was associated with age, disease stage and positive nodal status but not with menopausal status. Serum HER-2/neu levels were negatively related with hormone receptor positivity. INTERPRETATION & CONCLUSION: HER-2/neu serum test could be done more frequently in women with breast cancer irrespective of the hormone receptor status, to suggest modifications in systemic adjuvant therapy, including possibly the use of Herceptin.

Imatinib-induced optic neuritis in a patient of chronic myeloid leukemia.

Imatinib is presently the commonest prescribes drug for patients of chronic myelogenous leukemia (CML) in chronic phase (CP) worldwide. Its ocular side effects are little known. Optic neuritis caused by this drug has not been reported (Medline search). We describe perhaps the first case of optic neuritis caused by this drug.

A case of primary rhabdomyosarcoma of the breast.

Primary rhabdomyosarcoma of the breast is a rarely reported in adults, and it occurrence is mostly observed in children. We report a case of primary rhabdomyosarcoma of breast in a 40-year-old lady, who presented in early stage and is in complete remission after one year of treatment.

Malignant myelomatous pleural effusion-Is onset of effusion a new prognostic factor?

Malignant pleural effusion in myeloma (MMPE) is a rare terminal event; with a median survival is four months. All the patients usually have multiple poor prognostic factors and none of them (like beta 2-microglobulin, karyotype, Stage of disease, C-reactive protein etc.) correctly predicts the survival. We are reporting a series of five cases and evaluated the factors influencing the overall survival. All of our patients had a very good response to treatment and had a better survival compared to the reported cases so far. After reviewing the literature carefully we found that timing of development of pleural effusion is probably the most important prognostic factor. Those who develop effusion after some time lag form the initial treatment, will have a poor survival (median four months) compared to those who had effusion at the start of the disease.

Unusual metastasis in colorectal cancer.

Metastasis from colorectal carcinoma occurs by either lymphatic or hematogenous spread. The most common sites of colorectal metastasis are the liver and lung. Involvement of the skin, muscles and bones are quite rare. The prognosis in such patients is usually poor. Herewith, we are reporting a case of colonic carcinoma who had cutaneous metastasis, muscular involvement and diffuse skeletal metastasis. At the end, she had brain metastasis, but liver and lung involvement was not observed till the end.

Microscopic, cultural and molecular evidence of disseminated invasive aspergillosis involving the lungs and the gastrointestinal tract.

A patient with acute promyelocytic leukaemia developed invasive aspergillosis post chemotherapy during a pancytopenic episode, clinically involving the lungs and the gastrointestinal tract. Dichotomously branched septate fungal hyphae were demonstrated microscopically in stools and sputa. Cultures of the samples yielded Aspergillus flavus, which were identical by RFLP and random amplification of polymorphic DNA analyses and antifungal MICs, proving disseminated disease. To the best of the author's knowledge, this is the first time that boluses of fungal hyphae have been demonstrated microscopically in the stools of a patient with gastrointestinal aspergillosis.

A retrospective study of clinico-hematological and cytogenetic profile of erythroleukemia from South India.

Objective of the study is the retrospective evaluation of clinico-hematological and cytogenetic profile of patients with erythroleukemia (EL) in a south Indian population. Case records of all patients with acute myeloid leukemia seen in the Department of Medical Oncology at Kidwai Memorial Institute of Oncology, Bangalore, between January 1997 and December 2004 were reviewed. Clinical details were noted and slides were reviewed. A total of 326 AML patient were diagnosed of whom 14 patients had AML M6. Contribution of EL to all forms of AML was 4.3%. The mean age was 37.1+13.9 yrs (range: 16-65); most patients were in their 4th decade, with a male: female ratio of 3.67: 1. Mean duration of symptoms in the present series was 10.9+6.9 weeks. Cytogenetics were normal in 71% of cases, and minor abnormalities were observed in 21% of cases. As a conclusion relative low incidence of secondary EL, more frequent normal karyotype, and relatively younger age observed in our series makes the picture of EL in our subcontinent different from that in other series reported thus far.