Correlation of the Geriatric Assessment with Overall Survival in Older Patients with Cancer.

AIMS: Global guidelines recommend that all older patients with cancer receiving chemotherapy should undergo a geriatric assessment. However, utilisation of the geriatric assessment is often constrained by its time-intensive nature, which limits its adoption in settings with limited resources and high demand. There is a lack of evidence correlating the results of the geriatric assessment with survival from the Indian subcontinent. Therefore, the aims of the present study were to assess the impact of the geriatric assessment on survival in older Indian patients with cancer and to identify the factors associated with survival in these older patients. MATERIALS AND METHODS: This was an observational study, conducted in the geriatric oncology clinic of the Tata Memorial Hospital (Mumbai, India). Patients aged 60 years and older with cancer who underwent a geriatric assessment were enrolled. We assessed the non-oncological geriatric domains of function and falls, nutrition, comorbidities, cognition, psychology, social support and medications. Patients exhibiting impairment in two or more domains were classified as frail. RESULTS: Between June 2018 and January 2022, we enrolled 897 patients. The median age was 69 (interquartile range 65-73) years. The common malignancies were lung (40.5%), oesophagus (31.9%) and genitourinary (12.1%); 54.6% had metastatic disease. Based on the results of the geriatric assessment, 767 (85.4%) patients were frail. The estimated median overall survival in fit patients was 24.3 (95% confidence interval 18.2-not reached) months, compared with 11.2 (10.1-12.8) months in frail patients (hazard ratio 0.54; 95% confidence interval 0.41-0.72, P < 0.001). This difference in overall survival remained significant after adjusting for age, sex, primary tumour and metastatic status (hazard ratio 0.56; 95% confidence interval 0.41-0.74, P < 0.001). In the patients with a performance status of 0 or 1 (n = 454), 365 (80.4%) were frail; the median overall survival in the performance status 0-1 group was 33.0 months (95% confidence interval 24.31-not reached) in the fit group versus 14.4 months (95% confidence interval 12.25-18.73) in the frail patients (hazard ratio 0.50; 95% confidence interval 0.34-0.74, P = 0.001). In the multivariate analysis, the geriatric assessment domains that were predictive of survival were function (hazard ratio 0.68; 95% confidence interval 0.52-0.88; P = 0.003), nutrition (hazard ratio 0.64; 95% confidence interval 0.48-0.85, P = 0.002) and cognition (hazard ratio 0.67; 95% confidence interval 0.49-0.91, P = 0.011). DISCUSSION: The geriatric assessment is a powerful prognostic tool for survival among older Indian patients with cancer. The geriatric assessment is prognostic even in the cohort of patients thought to be the fittest, i.e. performance status 0 and 1. Our study re-emphasises the critical importance of the geriatric assessment in all older patients planned for cancer-directed therapy.

Validation of PREDICT Version 2.2 in a Retrospective Cohort of Indian Women With Operable Breast Cancer.

PURPOSE: Online prediction models that use known prognostic factors in breast cancer (BC) are routinely used to assist in decisions for adjuvant therapy. PREDICT Version 2.2 (P2.2) is one such online tool, which uses tumor size, lymph node involvement, grade, age, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, and Ki67. We performed an external validation in a retrospective cohort of patients treated at a tertiary center in India. METHODS: Women with operable BC between 2008 and 2016 with nonmetastatic, T1-T2 invasive, and HER2 receptor-negative BC and with available 5-year overall survival (OS) data were selected. Median predicted 5-year OS rates were used to calculate predicted events for the whole cohort and subgroups. The chi-square test was used to evaluate the goodness of fit of the tool. RESULTS: Of 11,760 cases registered between 2008 and 2016, 2,783 (23.66%) eligible patients with a median age of 50 (26-70) years and a median pT size of 2.5 (0.1-5) cm, 2,037 (73.19%) with grade 3 tumors, 1,172 (42.11%) with node-positive disease, 817 (29.35%) with triple-negative breast cancer, and 1,966 (70.64%) with HR-positive BC were included in the analysis. The observed 5-year OS and predicted 5-year OS in the whole cohort were 94.8% and 90.00%, respectively, with an absolute difference of 4.8% (95% CI, 3.417 to 6.198, P < .001). The observed 5-year OS and predicted 5-year OS were also different in various subgroups. CONCLUSION: PREDICT version 2.2 overestimated the number of deaths, with lower predicted 5-year OS compared with the observed value, in this retrospective Indian cohort. The reasons for this discrepancy could be differing biologic characteristics and possible selection bias in our cohort. We recommend a prospective validation of PREDICT in Indian patients and advocate caution in its use until such validation is achieved.

Accuracy of Intraoperative Frozen Section Analysis of Lymph Nodes in Women Undergoing Axillary Sampling for Treatment of Breast Cancer: Single Institution Audit.

BACKGROUND: Axillary lymph node (LN) positivity is an important prognostic factor in breast cancer. Almost 30% clinically node negative (cN0) early breast cancers have positive nodes on pathology, wherein an axillary dissection is done as a second stage surgery. Intra operative frozen section (FS) potentially avoids redo surgery. MATERIALS AND METHODS: We performed a retrospective audit for the false negative rate of intraoperative FS, from 2014 to 2018. All cN0 women undergoing upfront surgery, who underwent low axillary sampling (LAS) with FS were included. RESULTS: Of 22,854 breast cancer cases, 2230 underwent LAS, of which 877 were node positive. Intraoperative FS was negative in 1423/2230 (63.81%) cases, of which 71/1423 (4.98%) were false negative, and came positive on final histopathology report (HPR). These 71 women had a median of 5 nodes (mean 4.85) dissected on FS (range 1-12) with a median 1 (mean 1.3) node positive (range 1-6) on HPR. The sensitivity of FS was 91.89% (95% CI, 89.89-93.62), with a negative predictive value of 95.01% (95% CI, 93.84-95.97), accuracy of 96.73% (95% CI, 95.90-97.43) and false negative rate 4.98%. On logistic regression analysis, micrometastasis (Odds ratio (OR) 7.76, 95% CI, 3.49-17.25, P < .001) lobular histology (OR 2.50, 95% CI, 1.007-6.223, P = .04) and nodes dissected (OR 1.18, 95% CI, 1.07-1.30, P = .001) were associated with higher false negative FS, and extra nodal extension (OR 0.32, 95% CI, 0.18-0.57, P ≤ .001) with lower false negative FS. CONCLUSION: The high concordance between intraoperative FS and definitive histology, suggests it's routine use for Sentinel lymph node/LAS LN can help avoid a second surgery.

Unique challenges and outcomes of young women with breast cancers from a tertiary care cancer centre in India.

BACKGROUND: Young (≤40 years) breast cancers (YBC) are uncommon, inadequately represented in trials and have unique concerns and merit studying. METHODS: The YBC treated with a curative intent between 2015 and 2016 at our institute were analysed. RESULTS: There were 1228 patients with a median age of 36 (12-40) years; 38 (3.1%) had Stage I, 455 (37.1%) - II, 692 (56.3%) -III, and remaining 43 (3.5%) Stage IV (oligo-metastatic) disease; 927 (75.5%) were node positive; 422 (34.4%) were Triple negatives (TNBC), 331 (27%) were HER-2 positive. There were 549 (48.2%) breast conservations and 591 (51.8%) mastectomies of which 62 (10.4%) underwent breast reconstruction. 1143 women received chemotherapy, 617 (53.9%) received as neoadjuvant and 142 (23.1%) had pathological complete response; 934 (81.9%) received adjuvant radiotherapy. At the median follow-up of 48 (0-131) months, 5-year overall and disease-free survival was 79.6% (76.8-82.5) and 59.1% (55.8-62.6). For stage I, II, III and IV, the 5-year overall-survival was 100%, 86.7% (82.8-90.6), 77.3% (73.4-81.2), 69.7% (52.5-86.9) and disease-free survival was 94% (85.9-100), 65.9% (60.3-71.5), 55% (50.5-59.5), and 29.6% (14-45.2) respectively. On multivariate analysis, TNBC and HER-2+ subgroups had poorer survival (p = 0.0035). 25 patients had BRCA mutations with a 5-year DFS of 65.1% (95% CI:43.6-86.6). Fertility preservation was administered in 104 (8.5%) patients; seven women conceived and 5 had live births. Significant postmenopausal symptoms were present in 153 (13%) patients. CONCLUSION: More than half of the YBC in India were diagnosed at an advanced stage with aggressive features leading to suboptimal outcomes. Awareness via national registry and early diagnosis is highly warranted. Menopausal symptoms and fertility issues are prevalent and demand special focus.

Trends in breast and cervical cancer in India under National Cancer Registry Programme: An Age-Period-Cohort analysis.

BACKGROUND: Trend analysis in cancer quantifies the incidence rate and explains the trend and pattern. Breast and cervical cancers are the two most common cancers among Indian women which contributed 39.4 % to the total cancer in India for the year 2020. This study aimed to report the time trends in cancer incidence of breast and cervical cancer using Age-Period-Cohort (APC) model from five Population Based Cancer Registries (PBCRs) in India for the period of 1985-2014. METHOD: Age-Period-Cohort model was fitted to five PBCRs of Bangalore, Chennai, Delhi, Bhopal and Barshi rural for breast and cervical cancer for 25-74 age-groups. The Estimated Annual Percent Change (EAPC) was calculated. Rate Ratio (RR) of cohort effects were estimated with a constraint of period slope to be zero (p = 0) since cohort has a stronger association with incidence than period. RESULT: A significant increase was noted in breast cancer in all PBCRs (EAPC, Range: Delhi, 1.2 % to Bangalore, 2.7 %) while significant decrease in cervical cancer (EAPC, Range: Bangalore -2.5 % to Chennai, -4.6 %) from all the PBCRs including Barshi rural during the period. RR estimates for breast cancer showed increasing trend whereas cervical cancer showed decreasing trend in successive birth cohorts across all five PBCRs. CONCLUSION: In both breast and cervical cancers, a significant age, cohort and period effect was noted in Bangalore, Chennai and Delhi. Despite period effect, the cohort effect was predominant and it may be attributed to the generational changes in risk factors among cancer breast and cervix.

Can We Avoid Axillary Lymph Node Dissection (ALND) in Patients with 1-2 Positive Sentinel/Low Axillary Lymph Nodes (SLN/LAS+) in the Indian Setting?

The ACOSOG Z0011 study, heralded as a "practice changing" trial, suggested that women with T1-2 breast cancer with 1-2 SLN+, undergoing breast conservation therapy, need not be offered further ALND. However, whether these results are applicable to all women in the Indian setting, it remains debatable. A retrospective audit of all cN0 operated from 2013 to 2018 was conducted. We analyzed the percentage of additional LN positive (LN+) in the ALND group and compared it to the ACOZOG Z11 trial. Of the 2350 cN0 with EBC who underwent LAS, 687 (29%) had positive lymph nodes on final histopathology. Five hundred ninety-seven (86.9%) patients had 1-2 LN+, 40 (5.8%) patients had 3 LN+, and 50 (7.3%) had 4 or more nodes positive. Demographic features in the ACOSOG Z11 are different from those in our study, looking at ACOZOG Z11 versus our cohort-median pT 1.7 cm versus 3 cm, 45% micrometastasis versus 99.16% macrometastasis, and 28-30% grade 3 tumors versus 73.7%. In our cohort 31.82% of the 1-2 LN positive had additional LN+ on ALND. Keeping in mind the difference in clinicopathological features between our cohort and that of ACOZOG Z0011 and that 31.82% of women had additional LN+ on ALND, it may not be appropriate to apply the results of the ACOSOG Z0011 trial directly to our general population. Possibly, only a select subset of patients who match the trial population of the ACOSOG Z11 could be offered observation of the axilla and validated nomograms can be used to identify high-risk patients.

Pregnancy associated breast cancer (PABC): Report from a gestational cancer registry from a tertiary cancer care centre, India.

BACKGROUND: Pregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration. METHODS: The study (2013-2020) evaluated demographics, treatment patterns and outcomes of PABC. RESULTS: There were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n = 49) or adjuvant (n = 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19-35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2-100) and 56% (95% CI: 42-75.6%) and for metastatic 24% (95% CI: 10.1%-58.5%) respectively. Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n = 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones. CONCLUSION: Data from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs.

Transposition flap for the oncoplastic reconstruction of outer quadrant breast defects.

Plastic surgical principles are incorporated with breast conservation surgery (BCS) for cancer to improve aesthetic outcomes. In developing countries, average tumour size is larger at presentation resulting in larger resections often, including overlying skin. LD flap has been the workhorse of partial breast reconstruction. We present an easy and effective alternative to LD flap for carefully selected cases of outer quadrant breast tumours. We report 41 cases of local transposition flap from the lateral chest wall for oncoplastic restoration post BCS, performed between January 2016 and February 2020, at our institution. The median age was 49 years (28-63). Twenty-six patients underwent upfront surgery and 15 after neoadjuvant chemotherapy (NACT). The average pathological tumour size was 2.9 cm (median 2.7 and range 1.1-6) and 1.5 cm (median 1.8 and range 0-3.5) for upfront and post-NACT groups, respectively. The median volume of the resected specimen was 277.8 ml and 253.2 ml for upfront and post-NACT groups, respectively. Three patients (7.5%) had a microscopic positive margin requiring margin revision. Three (7.5%) patients had post-operative minor wound complications and were managed conservatively. At a median follow-up of 14 months (1-36), only 2/19 (10.5%) patients had clinical fat necrosis. Local transposition flap from the lateral chest wall based on dermal and subdermal plexus, carefully designed in selected patients, can be used effectively for the reconstruction of outer quadrant breast defects. It is easy to learn, offers good cosmetic outcome, avoids the morbidity and time of LD flap and saves LD flap for future use.

Does a less intensive surveillance protocol affect the survival of patients after treatment of a sarcoma of the limb? updated results of the randomized TOSS study.

AIMS: A single-centre prospective randomized trial was conducted to investigate whether a less intensive follow-up protocol would not be inferior to a conventional follow-up protocol, in terms of overall survival, in patients who have undergone surgery for sarcoma of the limb. Initial short-term results were published in 2014. PATIENTS AND METHODS: The primary objective was to show non-inferiority of a chest radiograph (CXR) group compared with a CT scan group, and of a less frequent (six-monthly) group than a more frequent (three-monthly) group, in two-by-two comparison. The primary outcome was overall survival and the secondary outcome was a recurrence-free survival. Five-year survival was compared between the CXR and CT scan groups and between the three-monthly and six-monthly groups. Of 500 patients who were enrolled, 476 were available for follow-up. Survival analyses were performed on a per-protocol basis (n = 412). RESULTS: The updated results recorded 12 (2.4%) local recurrences, 182 (36.8%) metastases, and 56 (11.3%) combined (local + metastases) recurrence at a median follow-up of 81 months (60 to 118). Of 68 local recurrences, 60 (88%) were identified by the patients themselves. The six-monthly regime (overall survival (OS) 54%, recurrence-free survival (RFS) 46%) did not lead to a worse survival and was not inferior to the three-monthly regime (OS 55%, RFS 47%) in terms of detecting recurrence. Although CT scans (OS 53%, RFS 54%) detected pulmonary metastasis earlier, it did not lead to a better survival compared with CXR (OS 56%, RFS 59%). CONCLUSION: The overall survival of patients who are treated for a sarcoma of the limb is not inferior to those followed up with a less intensive regimen than a more intensive protocol, in terms of frequency of visits and mode of imaging. CXR at six-monthly intervals and patient education about examination of the site of the surgery will detect most recurrences without deleterious effects on the eventual outcome. Cite this article: Bone Joint J 2018;100-B:262-8.

Activation of phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin pathway and response to everolimus in endocrine receptor-positive metastatic breast cancer - A retrospective pilot analysis and viewpoint.

INTRODUCTION: Biomarkers predictive of response to mechanistic target of rapamycin (mTOR) inhibitor, everolimus, in endocrine receptor (ER)-positive metastatic breast cancer (MBC) are a work in progress. We evaluated the feasibility of directly measuring mTOR activity and phosphatase and tensin homolog (PTEN) expression and correlating their expression with response and survival. MATERIALS AND METHODS: MBC patients who received everolimus with endocrine therapy (ET) after progression on an aromatase inhibitor and had adequate tissue preservation for estimation of mTOR activity and PTEN expression were selected for analysis from a prospectively maintained database. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method, and correlation between mTOR activity and PTEN expression with survival was done by log-rank test. RESULTS: Thirteen ER-positive MBC patients were available for analysis. PTEN expression was lost in 11/13 (84.6%) patients and retained in 2/13 patients (15.4%). mTOR activity was absent in four patients (30.7%), weak in six patients (46.1%), and moderate in 3 patients (23.2%). Median PFS for the entire population was 2.5 months while median OS was not reached. Patients with an absent mTOR activity showed a longer PFS (5 vs. 1.5 vs. 2 months) than those with weak and moderate activity, respectively (P = 0.043). There was no correlation between loss of PTEN expression and PFS. CONCLUSIONS: Measurement of direct mTOR activity in patients with MBC receiving everolimus/ET combination appears feasible. Absent mTOR activity may predict for longer PFS with everolimus-ET combination and requires further study.

Taxane Combination Chemotherapy in Breast Cancer: Experience from a Tertiary Cancer Centre in India.

AIMS: Docetaxel, Doxorubicin, Cyclophosphamide (TAC) is an intensive chemotherapy regimen; however, being highly myelosuppressive, its usage is limited in developing countries and hence merits exploration for feasibility and efficacy. MATERIALS AND METHODS: This was a retrospective audit of medical records of breast cancer patients receiving TAC chemotherapy) from 2004 to 2008. Demographic details, toxicity, and outcome analysis were carried out. RESULTS: A total of 133 patients (126 in [neo] adjuvant and 7 in metastatic setting) received TAC chemotherapy. The median age was 45 (21-67) years; 31% had coexisting diabetes and 12% hypertension. The delivered dose intensity was 94%. Discontinuation rate was 21/133 (15.8%) and the most common reason was hematological toxicity. There were 43 (32%) cases of febrile neutropenia and 2 (1.5%) Grade III thrombocytopenia with 3 (2%) toxic deaths. Grade III gastrointestinal toxicity (diarrhea) occurred in 35 (26%) and cardiac toxicity (congestive cardiac failure) in 2 (1.5%) patients. On univariate analysis, none of the variables (baseline serum albumin, hemoglobin, disease stage, or age) was found significant for chemotoxicity. At a median follow-up of 27 months (0.13-71.30 months), the estimated median disease-free survival (DFS) was 52 months in locally advanced group; however, the early breast cancer cohort has not reached to median DFS. CONCLUSIONS: TAC is an effective regimen but has significant toxicity despite the use of primary prophylactic Granulocyte Colony-Stimulating-Factor (G-GSF), including a small possibility of death. It can be considered "practically feasible" regimen in the adjuvant setting in carefully selected, fit patients.

Sentinel node biopsy versus low axillary sampling in women with clinically node negative operable breast cancer.

BACKGROUND: Sentinel node biopsy (SNB) was initially conceived as excision of the first station axillary lymph node(s) (LN) identified by radioactive and/or blue dye uptake. The definition was subsequently enlarged to also include palpable lymph nodes in the vicinity of sentinel node(s) (SN). We reasoned that the excision of this combination of nodes might be best achieved by sampling the lower axilla. METHODS: Each patient underwent low axillary sampling (LAS) and identification of SN in the excised specimen followed by complete axillary lymph node dissection (ALND). LAS was defined as excision of all fibrofatty tissue overlying the second digitation of serratus anterior below the intercostobrachial nerve and was carried out following a pre-operative injection of radioactive colloid and an intra-operative injection of blue dye. Blue and/or hot nodes (B&/HN) in the dissected tissue and remaining axilla, along with any palpable nodes within the sampled tissue, were defined as SN. The primary endpoint of the study was to compare false negative rates (FNR) of SN with that of LAS in predicting axillary LN status (NCT00128362). FINDINGS: The study was performed between March 2004 and December 2011 in 478 women with clinically node negative axilla. On histopathological evaluation the median tumor size was 2.5 cm and axillary nodal metastases were found in 34.1% of patients. The FNR of SNB (12.7%, 95% CI 8.1-19.4) and LAS (10.5%, 95% CI 6.6-16.2) were not significantly different (p = 0.56). The FNR of B&/HN alone, without palpable nodes, (29.0%, 95% CI 22.5-36.6) was significantly inferior to those of SNB (p = 0.0007) and LAS (p = 0.0003). INTERPRETATION: LAS is as accurate as SNB in predicting axillary LN status in women with clinically node negative operable breast cancer. Confining SNB procedure to excision of B&/HN, significantly increases the risk of leaving behind metastatic lymph nodes in the axilla. LAS is an effective and low cost procedure that minimizes axillary surgery and can be implemented widely. Registry Name: Clinicaltrials.gov. REGISTRATION NUMBER: NCT00128362.

Functional Radionuclide Imaging, In-Vitro Radioiodine Uptake Estimation and RT-PCR in the Evaluation of Sodium Iodide Symporter (NIS) Expression and Functionality in Breast Cancer: A Pilot Study.

Breast cancer is a common malignancy in females, which is considered as a systemic disease, whose treatment involves combined modality including systemic as well as local treatment. Recent studies have shown that breast cancer also expresses Sodium Iodide Symporter (NIS) gene, like in the thyroid, which is the factor responsible for the uptake of iodide by the thyroid, enabling radioiodine therapy of thyroid disorders. This study aimed to evaluate various radionuclide imaging characteristics, in vitro radioiodine uptake (RAIU) and evaluation of NIS expression by using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) to explore sodium iodide symporter (NIS) expression and iodine uptake in breast cancer and to explor e whether radioiodine can be used for the diagnosis and treatment of breast cancer. Ways of differential regulation of NIS expression in breast cancer has also been explored. Female patients with palpable breast lump and histologically proven infiltrating duct carcinoma were taken up for the study, which included 50 females of mean age 49 years. (range: 23-73 years). The patients were categorized into different groups, depending on the type of the study performed. The uptake patterns in various imaging modalities were analyzed and compared with invitro and RT-PCR studies. 68 % of breast cancer cases showed (99m)Tc-pertechnetate uptake at the initial images. This finding could partly be due to tumor vascularity, which is usually higher compared to the normal tissues. The uptake in the delayed imaging could be related to that due to NIS in the breast. Use of perchlorate or stable iodine did not alter the pertechnetate uptake pattern in breast tumor. Good correlation between (99m)Tc-pertechnetate and (99m)Tc-tetrofosmin uptake in breast cancer was demonstrated. In vitro radioactive iodine uptake in the breast tumor was significantly higher than that in the normal breast tissue. Only 42 % of breast tumor samples studied using RT-PCR showed NIS expression. Correlation between (99m)Tc-pertechnetate uptake and NIS expression could not be well established. Further studies with higher dose of radioiodine and/or mechanisms of differentially blocking the thyroid are required to assess the feasibility of radioiodine therapy for breast cancer.

Pathological complete response in locally advanced breast cancer: determinants and predictive significance.

BACKGROUND: Neoadjuvant chemotherapy is now the standard approach for most large breast cancers including locally advanced cancers of the breast. The majority of patients respond satisfactorily to chemotherapy with effective downsizing of tumours to consider breast conservation surgery. Pathological complete response (pathCR) is known to be a strong predictor of good outcome; however, many factors are known to influence the extent of response to chemotherapy. It has been observed that smaller the tumour, better is the response achieved in contrast to larger and locally advanced tumours where only one-third may respond well enough to merit breast conservation. Various other clinical, biological and molecular factors are also being evaluated as effective predictors of chemosensitivity. Most of these are either not easily available for all patients in developing countries or are overtly expensive and not applicable for all patients. METHODS: We evaluated the clinical and pathological predictors of response to chemotherapy in 1402 women with locally advanced breast cancer. RESULTS: There was a higher rate of pathCR in smaller tumours, younger women and ER-negative as well as triple negative tumours. The presence of ductal carcinoma in situ (DCIS) and lymphatic and vascular invasion (LVI) were associated with lower pathCR. CONCLUSION: In the absence of ready availability of expensive molecular and genomic assays, clinical parameters and standard histopathological variables can also be useful indicators of response to neoadjuvant chemotherapy. Additionally, they can help identify those who could be eventually conserved or have a better outcome.

Will the proposed compensation guidelines for research-related injury spell the death knell for clinical research in India?

The Indian Council of Medical Research and the Central Drugs Standards Control Organization of the Directorate General of Health Services of the Ministry of Health and Family Welfare' draft guidelines for compensation of research-related injury have evoked strong responses from the clinical research community. All stakeholders, including academic researchers, teachers in medical colleges, the pharmaceutical industry and even members of Institutional Review Boards and Ethics Committees have expressed grave reservations about several clauses in the guidelines. Moreover, these two guidelines differ from each other in important areas, reiterating that more thought and discussion is necessary to refine the guidelines. We present an academic researcher's perspective of the guidelines and our views on how they will affect clinical research in the country. The paper covers the types of research-related injury that are entitled for compensation, controversies on whether injury resulting from standard care should be entitled for compensation, whether causality needs to be established as a prerequisite for eligibility for compensation and whether all forms of research should have mandatory provision for compensation. We also put forward the potential dangers of such recommendations, which could potentially be inducement for patients to participate in clinical research. Finally, we raise the philosophical issue of infringement of an individual's fundamental rights regarding what research he/she wishes to participate in. While these points are based on several formal and informal discussions with stakeholders from various fields of clinical research, the views expressed are the authors' own personal thoughts.

Single agent weekly paclitaxel as neoadjuvant chemotherapy in locally advanced breast cancer: a feasibility study.

AIM: To study the toxicity profile and response rates of weekly paclitaxel given as neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer. MATERIALS AND METHODS: The study was planned as a single arm, prospective phase II study. Twenty-six patients with locally advanced breast cancer were enrolled in the study from December 2006 to October 2007. These patients underwent NACT with weekly paclitaxel at 100 mg/m(2) for 8 consecutive weeks followed by surgery. This was followed by anthracycline-based chemotherapy for three to four cycles followed by radiation. The patients received standard adjuvant hormonal therapy. The patients were carefully monitored for side-effects using common toxicity criteria. The clinical and pathological response rates were documented. The response rates were descriptively stated. RESULTS: The median age of the patients was 52 years (30-67 years) and the median tumour size was 7 cm (2.5-15 cm). Of the 208 planned weekly cycles, 207 could be given. The rates of grade 3-4 neutropenia, thrombocytopenia and neuropathy were 4, 12 and 4%, respectively. A complete clinical response was observed in 10 patients (38.5%) and a completed pathological response, defined as the absence of invasive cancer from the breast and axillary nodes, was seen in 11.5% of patients. Breast-conserving surgery was possible in 23% of patients. CONCLUSION: The regimen of weekly single agent paclitaxel is feasible in patients with locally advanced breast cancer with acceptable toxicity. It resulted in a pathological response rate that was comparable with other regimens in this group of advanced stage patients. Considering the efficacy and low toxicity of this regimen, it is worth exploring in larger studies.

Cancer survival in Barshi, India, 1993-2000.

The rural cancer registry of Barshi, Paranda and Bhum, was the first of its kind in India and was established in 1987. Registration of cases is carried out entirely by active methods. Data on survival from 15 cancer sites or types registered during 1993-2000 are reported in this study. Follow-up has been carried out predominantly by active methods, with median follow-up time ranging between 2-49 months for different cancers. The proportion of histologically verified diagnosis for various cancers ranged between 73-98%; death certificates only (DCOs) comprised 0-2%; 98-100% of total registered cases were included for survival analysis. Complete follow-up at five years ranged between 96-100% for different cancers. The 5-year age-standardized relative survival rates for selected cancers were non-melanoma skin (86%), penis (63%), breast (61%), cervix (32%), mouth (23%), hypopharynx (11%) and oesophagus (4%). The 5-year relative survival by age group did not display any particular pattern. Five-year relative survival trend between 1988-1992 and 1993-2000 showed a marked decrease for cancers of the tongue, hypopharynx, stomach, rectum, larynx, lung and penis; but a notable increase for breast and non-Hodgkin lymphoma.