Ten-year survival outcome of breast cancer patients in India.

INTRODUCTION: Breast cancer is the most frequently diagnosed cancer among women in India; however, there are no studies addressing long-term survival (10 years and above). This study sought to evaluate long-term oncological outcome among women with breast cancer treated with a curative intent. MATERIALS AND METHODS: This is a retrospective cohort analysis of 1301 breast cancer patients of all stages who had received primary treatment with curative intent from 2004 to 2010 at a single cancer institution of India. RESULTS: A total of 1301 breast cancer patients were available for final analysis. The median age was 51 years (range, 21-86 years). 70.25% of the patients had early breast cancer (EBC), 21.9% had locally advanced breast cancer, and 7.85% of the patients with de novo metastatic disease also underwent surgery. 56.5% of the patients had hormone-sensitive tumors, human epidermal growth factor receptor 2 over expression was seen in 17%, and triple-negative tumors accounted for 26.2% of the patients. The 5- and 10-year overall survival (OS) of the entire cohort was 79% and 66%, and the 5- and 10-year breast cancer-specific survival (BCSS) was 79% and 70%, respectively. OS and BCSS were 51% and 58%, respectively, at 15-year follow-up after primary cancer treatment. On multivariate analysis, the factors associated with prolonged survival were age ≤50 years, EBC, and treatment during the later period (2008-2010). CONCLUSION: Difference between OS and BCSS was found to have an increasing trend during 10-15-year follow-up, the difference being 4% at 10 years and 7% at 15 years. Age ≤50 years, early-stage disease at presentation, and primary cancer treatment in later years (2008-2010) were favorable predictors for 10-year survival.

A comparative study on erlotinib & gefitinib therapy in non-small cell lung carcinoma patients.

Background & objectives: Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) have been evaluated in patients with advanced non-small cell lung cancer (NSCLC). Erlotinib and gefitinib are the first-generation EGFR-TKIs for patients with NSCLC. However, there is a paucity of studies comparing the effectiveness of these two drugs. Hence, this study was aimed to compare the effectiveness and safety of erlotinib and gefitinib in NSCLC patients. Methods: This study included 71 NSCLC patients who received EGFR-TKIs between 2013 and 2016. Adverse drug reaction of both erlotinib (n=37) and gefitinib (n=34) was determined and graded according to Common Terminology Criteria for Adverse Events grading system. Effectiveness was measured using response evaluation criteria in solid tumours and progression-free survival (PFS). Pharmacoeconomic analysis was performed by cost-effective analysis. Results: When comparing safety profile, both the drugs had similar adverse events except for dermal side effects such as acneiform eruption (51.4%), rash (54.05%) and mucositis (59.5%) for erlotinib and 20.6, 26.5 and 29.4 per cent for gefitinib, respectively. The PFS of the two drugs was compared to differentiate the effectiveness of erlotinib and gefitinib. There was no significant difference between the effectiveness of the two drugs. The pharmacoeconomic analysis showed that gefitinib was more cost-effective than erlotinib. Interpretation & conclusions: This study showed that erlotinib and gefitinib had similar effectiveness but gefitinib had a better safety profile compared to erlotinib. Therefore, gefitinib could be considered a better option for NSCLC patients compared to erlotinib. However, further studies need to be done with a large sample to confirm these findings.

Short-course lenalidomide plus low-dose dexamethasone in the treatment of newly diagnosed multiple myeloma-a single-centre pragmatic study.

PURPOSE: We assessed response to treatment, toxicity, time to progression, progression-free survival, and overall survival in patients newly diagnosed with multiple myeloma who were ineligible for or unwilling to undergo transplantation and who were treated with a combination of lenalidomide and low-dose dexamethasone for a fixed 6 cycles in a resource-constrained environment. METHODS: This pragmatic study, conducted in a single tertiary cancer centre in South India, enrolled patients from May 2009 till April 2011. Treatment included lenalidomide 25 mg daily for 21 days, with dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day cycle, for 6 cycles. Response was evaluated after the 3rd and 6th cycles of treatment. All patients were followed for 5 years. RESULTS: The study enrolled 51 patients. Median age in the group was 61 years (range: 38-76 years). Immunoglobulin G or A myeloma constituted 70.6% of the diagnoses, and light-chain myeloma constituted 29.4%. Stages i, ii, and iii (International Staging System) disease constituted 21.4%, 28.6%, and 50% of the diagnoses respectively. All patients were transplantation-eligible, but 34 (66.7%) refused for economic reasons. After treatment, 19.6% of the patients achieved a stringent complete response; 35.3%, a complete response; 5.9%, a very good partial response; and 29.4%, a partial response, for an overall response rate of 90.2%. Stable disease was seen in 3.9% of patients, and progressive disease, in 5.9%. Grade 3 or greater nonhematologic and hematologic toxicity occurred in 35.2% and 11.7% of patients respectively. Pulmonary embolism occurred in 1 patient. No patient experienced deep-vein thrombosis or peripheral neuropathy. The median follow-up duration was 66 months. All patients experienced disease progression. Median progression-free survival was 16 months. In 10 patients, re-challenge with lenalidomide and dexamethasone achieved a second complete response. At the time of writing, 19 patients had died. The overall survival rate at 5 years was 62.74%. Median overall survival is not yet reached. CONCLUSIONS: In a resource-constrained setting, lenalidomide with low-dose dexamethasone is an effective treatment with acceptable toxicity in patients newly diagnosed with multiple myeloma and not planned for transplantation. Complete responses were significantly more frequent than reported in the Western literature. Occurrence of clinical deep-vein thrombosis was rare, but hyperglycemia was common. An abbreviated course of treatment is suboptimal in multiple myeloma. Maintenance regimens should be advocated.

Integrative management of insomnia during cancer chemotherapy: A case report.

INTRODUCTION: Insomnia is common among cancer patients, affecting about 50% undergoing cancer treatment. Insomnia can be due to various reasons, such as physical-pain, psychological-distress and medication side-effects. Insomnia has significant impact on quality of life of cancer patients. Even-though managed with hypnotics and antipsychotic drugs, they cause dependency with various short-term and long-term complications. Presenting a case throwing light on Ayurveda topical intervention as add-on to standard-of-care in insomnia during cancer chemotherapy. METHOD: A 51-year-old female patient with breast-cancer with extensive necrosis extending to subcutaneous areas was due for second cycle chemotherapy and was diagnosed with moderate-insomnia with a score of 21 as per Insomnia Severity Index in the Out-Patient-Department. Quality of sleep was assessed using Pittsburgh-Sleep-Quality-Index. Treated for 14 days during the break between cycle two and cycle three with Shirothalam (applied on the vertex) using Kachuradi Churnam with Kshirabala 101 and Padabhyangam (foot massage) using Kshirabala thailam as add-on to Tab Zolpidem5mg. Assessment was conducted on baseline and after 14 days of intervention. RESULTS: Assessment for insomnia before and after intervention was conducted with Insomnia-Severity-Index. The score improved from 21 to 2. Quality of sleep before and after intervention was assessed using global PSQI. It improved from 20 to 8. DISCUSSION: In Ayurveda, Nidranasam (loss of sleep) results from aggravation of Vata-Pitta (body humors responsible for movement and cognition and digestion, metabolism and heat of body), depletion of Kapha (body humor responsible for structural cohesion of body), derangement of Manasika-Dosa (mental constituents) and other diseases. All these etiological factors are attributed by Tikshna(sharp)- Ushna(hot potency) and Ruksha(dry) chemotherapy regimens. Vata-Pitta-hara (normalising Vata and Pitta) and Indriyaprasadaka (clearing senses) action of medicines used could induce sleep and effectively improve quality of sleep. CONCLUSION: Integrative-intervention was found to be beneficial in improving insomnia and quality of sleep without any reported complications or dependency in this case. After 14 days of ayurvedic intervention, the patient could get sleep even without taking zolpidem 5mg and external therapies. Same protocol could be considered for generalization so that it could modify or reduce usage of hypnotics and antipsychotic-drugs.

Revisiting the outstanding questions in cancer nanomedicine with a future outlook.

The field of cancer nanomedicine has been fueled by the expectation of mitigating the inefficiencies and life-threatening side effects of conventional chemotherapy. Nanomedicine proposes to utilize the unique nanoscale properties of nanoparticles to address the most pressing questions in cancer treatment and diagnosis. The approval of nano-based products in the 1990s inspired scientific explorations in this direction. However, despite significant progress in the understanding of nanoscale properties, there are only very few success stories in terms of substantial increase in clinical efficacy and overall patient survival. All existing paradigms such as the concept of enhanced permeability and retention (EPR), the stealth effect and immunocompatibility of nanomedicine have been questioned in recent times. In this review we critically examine impediments posed by biological factors to the clinical success of nanomedicine. We put forth current observations on critical outstanding questions in nanomedicine. We also provide the promising side of cancer nanomedicine as we move forward in nanomedicine research. This would provide a future direction for research in nanomedicine and inspire ongoing investigations.

Antibody-drug conjugate as targeted therapeutics against hepatocellular carcinoma: preclinical studies and clinical relevance.

An antibody-drug conjugate (ADC) is an advanced chemotherapeutic option with immense promises in treating many tumor. They are designed to selectively attack and kill neoplastic cells with minimal toxicity to normal tissues. ADCs are complex engineered immunoconjugates that comprise a monoclonal antibody for site-directed delivery and cytotoxic payload for targeted destruction of malignant cells. Therefore, it enables the reduction of off-target toxicities and enhances the therapeutic index of the drug. Hepatocellular carcinoma (HCC) is a solid tumor that shows high heterogeneity of molecular phenotypes and is considered the second most common cause of cancer-related death. Studies show enormous potential for ADCs targeting GPC3 and CD24 and other tumor-associated antigens in HCC with their high, selective expression and show potential outputs in preclinical evaluations. The review mainly highlights the preclinical evaluation of different antigen-targeted ADCs such as MetFab-DOX, Anti-c-Met IgG-OXA, Anti CD 24, ANC-HN-01, G7mab-DOX, hYP7-DCand hYP7-PC, Anti-CD147 ILs-DOX and AC133-vcMMAF against hepatocellular carcinoma and its future relevance.

Disseminated peritoneal leiomyosarcomas after laparoscopic "myomectomy" and morcellation.

Herein is reported a case of disseminated peritoneal leiomyosarcoma arising shortly after laparoscopic myomectomy and specimen retrieval with an electromechanical morcellator. The topography of the sarcomas suggests morcellation as a contributing factor. This case shows that caution should be exercised when selecting patients for laparoscopic myomectomy and stresses the need for a thorough pathologic examination of the specimen retrieved.

Impact of St. Gallen surrogate classification for intrinsic breast cancer sub-types on disease features, recurrence, and survival in South Indian patients.

BACKGROUND: Breast cancer is a heterogeneous group of disease, and recently, intrinsic sub-typing on the basis of gene expression profiling is found to be a predictor of breast cancer clinical course. The St. Gallen has released surrogate classification for breast cancer sub-types depending on immunohistochemistry (IHC) markers. AIM: The aim of our study was to analyze the distribution of sub-types using IHC surrogate markers in our patient population and to assess the clinico-pathological factors in different sub-types. MATERIALS AND METHODS: A total of 635 non-metastatic patients who underwent radical intend treatment from January 2011 to December 2013 were included for this retrospective analysis. A statistical analysis was done by Windows SPSS version 20. The Chi-square test was used to examine the correlations of these sub-types with clinico-pathological parameters. The Kaplan-Meier method estimates were used for survival analysis. RESULTS: The median follow-up was 42.77 months (5 months to 112 months). Luminal B was the predominant group. Disease free survival (DFS) at 5 years was 95% in luminal A, 78% in luminal B HER-2 negative, 80% in luminal B HER-2 positive, 72% in triple negative, and 79% in HER-2/neu non-luminal. Tumor size, Ki67, T stage, N stage, and grade were significantly associated with DFS in all biological type with a P value of less than 0.05. CONCLUSION: Surrogate classification was successfully applied in our patient cohort. Luminal B and triple negative sub-groups were more prevalent in our patients, and this finding is at variance with published international data. Biological sub-type also emerged as an important predictor of survival.

Primary Tumor Location as a Prognostic and Predictive Marker in Metastatic Colorectal Cancer (mCRC).

Clinico-pathological differences between adenocarcinoma in the right and left colo-rectum play a role in determining the prognosis and response to treatment. Studies suggest that primary tumor location is more relevant as the disease progresses and reflects a possible difference in biology and response to therapy. This review aims to explore the clinico-pathological features of right and left colo-rectum and the impact of primary tumor location on prognosis of CRC as well as discuss the available clinical data on tumor sidedness in metastatic colorectal cancer. In so far as the clinical data of tumor sidedness is concerned, very few reviews have discussed the clinical implications of sidedness in heavily pre-treated metastatic colorectal cancer (second and subsequent lines of therapy in metastatic disease). This review aims to fill the current gap in this setting.

A pilot study to assess the feasibility of evaluation of markers of response to chemotherapy at one day & 21 days after first cycle of chemotherapy in carcinoma of breast: a prospective non-randomized observational study.

BACKGROUND: Interest in translational studies aimed at investigating biologic markers in predicting response to primary chemotherapy (PCT) in breast cancer has progressively increased. We conducted a pilot study to evaluate feasibility of evaluating biomarkers of response to PCT at one & 21 days after first cycle. METHODS: Adult, non-pregnant, non-lactating women with histologically confirmed infiltrating duct carcinoma underwent serial core biopsies after first cycle of PCT and these were scored for Ki-67, Bcl-2 and Caspase-3 using immunohistochemistry. RESULTS: We recruited 30 patients with a mean age of 51 years. We were successful 95.6% times in performing a core biopsy and of these 84.6% had adequate tissue in the cores harvested. After a mean of 4 cycles of PCT, 26 patients underwent surgery and good response was noted in 9 patients (30%) using Miller-Payne criteria. There was a trend noted in all markers, which appeared different in those with good response and poor response. Good responders had significantly higher Ki-67 and significantly lower Bcl-2 at baseline and a significant decrease in Ki-67 and Caspase-3 at 21 days after the first chemotherapy. CONCLUSION: We report a detectable change in biomarkers as early as 24-48 hours after the first chemotherapy along with a definite trend in change that can possibly be used to predict response to chemotherapy in an individual patient. The statistical significance and clinical utility of such changes needs to be evaluated and confirmed in larger trials.

A Study on the Clinical Outcome of Abiraterone Acetate in Castration Resistant Prostate Cancer Patients.

Background: Abiraterone acetate was approved by FDA and EMA in April and September 2011, respectively for treatment of patients with casteration resistant prostate cancer and those previously treated with docetaxel. It is a selective inhibitor of androgen biosynthesis which potentially and irreversibly blocks CYP17, a crucial enzyme in oestrogen and testosterone synthesis. Materials and Methods: This retrospective study was conducted to evaluate the safety and efficacy of abiraterone acetate in the treatment of castration resistant prostate cancer patients. Twenty-two male patients diagnosed with CRPC and experienced treatment failure with one or more lines of treatment (hormonal manipulation or chemotherapy) were selected and administered abiraterone acetate (1,000 mg daily) along with prednisone (5 mg twice daily). Results: Out of 22 patients, 32% had a good response in reduction of PSA values, while 22% had progression in disease and 45% had a stable disease. Potassium, Haemoglobin, and serum sreatinine levels were not affected by the drug. Due to severe GI intolerance, the drug had to be stopped for one patient. The results of this study showed that abiraterone acetate significantly lowered the PSA values and prolonged progression- free survival in metastatic castration resistant prostate cancer patients who had progressed after first-line or second-line treatment. The overall average median survival and the median duration of drug exposure for CRPC who received AA was found to be 11.1 months [range 3-18]. Since AA plus prednisolone are available as oral dosage forms, they can be given in outpatient setting. Conclusion: Abiraterone acetate is a drug of choice for CRPC and also for those who had previously received one or two chemotherapy regimens. Since it is a new therapeutic regimen, this study included small sample size, but there are a few studies indicating the therapeutic efficacy of AA among patients with castration-resistant prostate cancer.

Antibody–drug conjugate as targeted therapeutics against hepatocellular carcinoma: preclinical studies and clinical relevance

An antibody–drug conjugate (ADC) is an advanced chemotherapeutic option with immense promises in treating many tumor. They are designed to selectively attack and kill neoplastic cells with minimal toxicity to normal tissues. ADCs are complex engineered immunoconjugates that comprise a monoclonal antibody for site-directed delivery and cytotoxic payload for targeted destruction of malignant cells. Therefore, it enables the reduction of off-target toxicities and enhances the therapeutic index of the drug. Hepatocellular carcinoma (HCC) is a solid tumor that shows high heterogeneity of molecular phenotypes and is considered the second most common cause of cancer-related death. Studies show enormous potential for ADCs targeting GPC3 and CD24 and other tumor-associated antigens in HCC with their high, selective expression and show potential outputs in preclinical evaluations. The review mainly highlights the preclinical evaluation of different antigen-targeted ADCs such as MetFab-DOX, Anti-c-Met IgG-OXA, Anti CD 24, ANC–HN-01, G7mab-DOX, hYP7-DCand hYP7-PC, Anti-CD147 ILs-DOX and AC133-vcMMAF against hepatocellular carcinoma and its future relevance.

Cranial neuropathy and bone involvement in primary systemic amyloidosis.

Bone involvement in primary systemic amyloidosis is rare. Intracranial involvement in primary amyloidosis has not been reported so far. We report two cases of bone involvement in primary amyloidosis. The first patient also had combined deficiencies of factor IX and XII, while the second patient had associated intracranial involvement and XIIth cranial nerve palsy. Both these cases are unique in that, destructive bone lesions with intracranial involvement and combined factor deficiencies have not been reported in primary amyloidosis previously.

Esthesioneuroblastoma with intracranial extension: A non-surgical approach.

Esthesioneuroblastoma is a rare tumor arising from the olfactory mucosa of upper respiratory tract. The primary modality of treatment has been surgery with craniofacial resection followed by post-operative radiotherapy. There are only a few reported cases of non-surgical approaches. We report a case of esthesioneuroblastoma with intracranial extension treated with Vincristine, Adriamycin, Cyclophosphamide, Ifosfamide, Etoposide protocol followed by radiation with 5 years of follow-up. This is the first reported case using this chemotherapy schedule.

Surgical treatment pattern and outcomes in epithelial ovarian cancer patients from a cancer institute in Kerala, India.

OBJECTIVE: To evaluate the treatment and survival pattern of patients with advanced epithelial ovarian cancer. METHODS AND RESULTS: Retrospective study of all advanced epithelial ovarian cancer patients treated in the department of gynaecologic oncology from an academic centre, in a four year period from 1 January 2008-31 December 2011. SELECTION CRITERIA: All patients with advanced epithelial ovarian cancer (stage III and IV) who underwent surgery from 2008-2011and had a follow-up of at least three months after completion of treatment were included. The decision on whether primary surgery or neoadjuvant chemotherapy (NACT) in advanced ovarian cancer was based on age, performance status, clinical and imaging findings. RESULTS: A total of 178 cases of epithelial ovarian cancer were operated on during this four year period. Among them 28 patients were recurrent cases, 22 had early stages of ovarian cancer, and the rest 128 had stage III and IV ovarian cancer. In these 128 patients, 50(39.1%) underwent primary surgery and 78(60.9%) had NACT followed by surgery. In the primary surgery group 36(72.0%) patients had optimal debulking while in the NACT group 59(75.6%) patient had optimal debulking. With a median follow-up of 34 months, the median overall survival (OS) and progression free survival (PFS) was 53 and 49 months respectively. Patients who underwent primary surgery had better median PFS than patients who had NACT (56 months versus 39 months, p = 0.002). In stage III C the difference median PFS was significant for those treated with primary surgery when compared with NACT (55 months versus 39 months, p = 0.012). In patients who had optimal debulking to no residual disease (n = 90), primary surgery gave a significant improved PFS (59 months versus 38 months, p = 0.001) when compared with NACT. In univariate analysis, NACT was associated with increased risk of death (HR: 0.350; CI: 0.177-0.693). CONCLUSION: In advanced epithelial ovarian cancer, primary surgery seems to have a definite survival advantage over NACT in patients who can be optimally debulked to no residual disease.

A prospective comparison of perioperative morbidity in advanced epithelial ovarian cancer: Primary versus interval cytoreduction - experience from India.

OBJECTIVES: The objective was to compare perioperative morbidity and mortality of patients with advanced epithelial ovarian cancer (EOC) treated with either of the two treatment approaches; neoadjuvant chemotherapy (NACT) followed by interval debulking versus upfront surgery. DESIGN: Prospective comparative observational study. PARTICIPANTS: In total, 51 patients were included in the study. All patients with diagnosed advanced EOC (International Federation of Gynecology and Obstetrics IIIC and IV) presenting for the 1(st) time were included in the study. INTERVENTIONS: Patients were either operated upfront (n = 19) if deemed operable or were subjected to NACT followed by interval debulking (n = 32). PRIMARY AND SECONDARY OUTCOMES: Intra- and postoperative morbidity and mortality were the primary outcome measures. RESULTS: Patients with interval cytoreduction were noted to have significantly lesser operative time, blood loss, and extent of surgery. Their discharge time was also significantly earlier. However, they did not differ from the other group vis. a vis. postoperative complications or mortality. CONCLUSIONS: Neoadjuvant chemotherapy although has a positive impact on various intraoperative adverse events, fails to show any impact on immediate postoperative negative outcomes.

Palatal palsy in a case of lepromatous leprosy.

A male patient with lepromatous leprosy developed nasal regurgitation of food due to palatal palsy during Type 2 reaction. Early high-dose administration of corticosteroid achieved a prompt therapeutic response and he completely recovered from palatal palsy. The associated lagophthalmos, foot drop and ulnar paralysis persisted.

Chronic myeloid leukemia presenting as gout.

A 53-year-old man presented with gouty arthritis. A physical examination and haematological and biochemical tests showed that he had chronic myeloid leukemia. He was treated with allopurinol, hydroxyurea and analgesics. The arthritis subsided completely within 2 weeks. He continues in haematologic remission (on interferon) with no further recurrence of the gout.

Cold haemagglutinin disease in systemic lupus erythematosus.

A 34-year-old lady presenting with features of cold agglutinin disease during the course of systemic lupus erythematosus is described. Cold antibody titer was very high (1 in 4096) with specificity for 'I' antigen. Even though she had poor prognostic factors like high titer of cold antibodies with low thermal amplitude, she responded well to prednisolone.

Acute myocardial infarction in north Kerala--a 20 year hospital based study.

This is a retrospective study of patients with first attack of myocardial infarction admitted to Medical College Hospital, Calicut during the years 1969 to 1988. The data analysed were compared to other hospital based studies in India and abroad. A striking increase in the percentage of acute myocardial infarction was observed. There was also an increase in the occurrence of myocardial infarction in the young. A properly designed population based study is warranted.