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Aims and Objectives: The ongoing COVID-19 pandemic is having a profound impact on the current clinical trials. We wanted to document the extent of the disruption amongst Indian clinical trial sites. Materials and Methods: We conducted an online survey among oncologists in India with active trials to document their experience with challenges and novel solutions. Results: A total of 60 oncologists replied of which 40 had ongoing trials with open recruitment. Majority of them had stopped screening (55%) and recruitment (62.5%). Almost half of the sites did not have adequate infrastructure (47.5%). Almost all the sites had enrolled patients worried about the impact of COVID-19 on their health outcome (up to 87.5%). The majority of sites had problems with adherence to study schedule of events (87.5%) and administration of study medication (42.5%). A total of 55% of the sites had provided the option of virtual visits. Both investigators (75%) and sponsors/contract research organizations (67.5%) had reached out to each other to maintain study integrity. More than half the centers had difficulty related to adverse events and serious adverse events (documentation and reporting; up to 75%). Discussion: Regulatory authorities in several countries have announced guidelines on the conduct of clinical trials during the COVID-19 pandemic. Whether the disruption lasts for a short or long time, its impact on clinical trials is going to be irreparable.

The Complement 1 trial investigated the efficacy and safety of ofatumumab + chlorambucil with chlorambucil monotherapy in patients with previously untreated chronic lymphocytic leukaemia (CLL). On long-term follow-up in the chemoimmunotherapy arm vs. the chemotherapy arm there was an estimated 12% (not significant) and 39% risk reduction in overall survival and progression-free survival, respectively. A high rate (61%) of treatment with next-line therapies in both the treatment arms may dilute any potential OS difference and confound the interpretation of the OS results. Addition of ofatumumab to chlorambucil demonstrated clinical benefit and tolerability as a frontline treatment option in patients unfit for fludarabine-containing therapy, with no new safety concerns.

Next generation sequencing studies in Chronic lymphocytic leukemia (CLL) have revealed novel genetic variants that have been associated with disease characteristics and outcome. The aim of this study was to evaluate the prognostic value of recurrent molecular abnormalities in patients with CLL. Therefore, we assessed their incidences and associations with other clinical and genetic markers in the prospective multicenter COMPLEMENT1 trial (treatment naive patients not eligible for intensive treatment randomized to chlorambucil (CHL) vs. ofatumumab-CHL (O-CHL)). Baseline samples were available from 383 patients (85.6%) representative of the total trial cohort. Mutations were analyzed by amplicon-based targeted next generation sequencing (tNGS). In 52.2% of patients we found at least one mutation and the incidence was highest in NOTCH1 (17.0%), followed by SF3B1 (14.1%), ATM (11.7%), TP53 (10.2%), POT1 (7.0%), RPS15 (4.4%), FBXW7 (3.4%), MYD88 (2.6%) and BIRC3 (2.3%). While most mutations lacked prognostic significance, TP53 (HR2.02,p

Background: MONALEESA-7 (NCT02278120), the first large randomized phase III clinical trial dedicated to investigating a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus ET vs ET + placebo (PBO) in pre- or perimenopausal patients with HR+/HER2− ABC, previously demonstrated a statistically significant improvement in OS with the addition of ribociclib (RIB) to ET vs PBO + ET (median, not reached vs 40.9 months; HR, 0.71 [95% CI, 0.54-0.95]; P = .00973; Im SA, et al. N Engl J Med. 2019). This concluded the protocol-defined final analysis of OS and the patients and investigators were unblinded to their treatment assignment allowing patients on the PBO arm to cross-over to RIB treatment. Longer follow-up allows for more events to further characterize the long-term survival benefits. Here we report an exploratory update of OS after a minimum of ~ four years of follow-up, an additional 20 months since the last report. Methods: Pre- or perimenopausal patients with HR+/HER2− ABC were randomized 1:1 to receive RIB or PBO plus goserelin with either a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole) or tamoxifen. RIB is approved in combination with an NSAI in pre- or perimenopausal patients. Patients who had received a prior CDK4/6i or ET in the advanced setting were excluded. Patients who received ET in the (neo)adjuvant setting or ≤ 1 prior line of chemotherapy for advanced disease were eligible to enroll. Updated OS were evaluated by Cox proportional hazards model and summarized using Kaplan-Meier methods. Additional post-progression endpoints such as progression-free survival 2 (PFS2), time to chemotherapy (CT) and CT-free survival were also evaluated and summarized. Results: The data cutoff for this updated OS analysis was 29 June 2020, and the median follow-up was 53.5 mo (min, 46.9 mo). These updated results with extended follow-up demonstrated an OS benefit with RIB + ET vs PBO + ET (median, 58.7 vs 48.0 mo; HR, 0.76 [95% CI, 0.61-0.96]). In patients receiving an NSAI, a similar OS benefit was observed with RIB + NSAI vs PBO + NSAI (median, 58.7 vs 47.7 mo; HR, 0.80 [95% CI, 0.62-1.04]). The survival benefit shown in subgroup analyses was consistent with the intent-to-treat (ITT) population. PFS2, time to chemotherapy (CT), and CT-free survival for the ITT and NSAI populations are in the Table. Among the patients who discontinued study treatment, 77.3% and 78.1% in the RIB + ET vs PBO + ET arms received a subsequent antineoplastic therapy, respectively, and 12.9% and 26.1% received a subsequent line of CDK4/6i. Additionally there were 15 patients in the PBO arm that crossed over to the RIB arm following unblinding and prior to disease progression. Conclusions: With an extended follow-up of more than 4 years, RIB + ET continued to demonstrate a clinically relevant OS benefit compared with ET alone in pre- or perimenopausal patients with a median OS ~5 years with RIB +ET in HR+/HER2− ABC. A similar benefit with RIB was observed for PFS2, time to CT, and CT-free survival. ITTNSAI cohortRIB + ETn=335PBO + ETn=337RIB + NSAIn=248PBO + NSAIn=247PFS2Events, n (%)177 (52.8)221 (65.6)131 (52.8)159 (64.4)Median, mo44.231.043.630.4HR (95% CI)0.68 (0.56-0.83)0.69 (0.55-0.87)Time to first CTEvents, n (%)144 (43.0)173 (51.3)107 (43.1)129 (52.2)Median, mo50.936.850.936.0ITT HR(95% CI)0.69 (0.56-0.87)0.66 (0.51-0.85)CT-free survivalEvents, n (%)190 (56.7)236 (70.0)139 (56.0)169 (68.4)Median, mo42.426.442.525.9HR (95% CI)0.67 (0.55-0.81)0.64 (0.51-0.81) Citation Format: Debu Tripathy, Seock-Ah Im, Marco Colleoni, Fabio Franke, Aditya Bardia, Nadia Harbeck, Sara Hurvitz, Louis Chow, Joohyuk Sohn, Keun Seok Lee, Saul Campos-Gomez, Rafael Villanueva Vazquez, Kyung Hae Jung, K Govind Babu, Paul Wheatley-Price, Michelino De Laurentiis, Young-Hyuck Im, Sherko Kümmel, Nagi El-Saghir, Mei-Ching Liu, Sharonjeet Kaur, Claudia Gasch, Craig Wang, Yongyu Wang, Arunava Chakravartty, Yen-Shen Lu. Updated overall survival (OS) results from the phase III MONALEESA-7 trial of pre- or perimenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD2-04.

Background: Synovial sarcoma represents 8% of all soft-tissue sarcoma (STS). It is a high-grade STS, and 50% of patients develop metastasis. The most common site of metastasis is the lungs, lymph nodes followed by bones. Ifosfamide-based chemotherapy is associated with improved outcome. In this study, we report our experience of metastatic synovial sarcoma according to primary sites, metastatic pattern, and their outcome. Materials and Methods: This was a retrospective observational study carried out at our institute from January 2013 to December 2016. The aim of our study was to evaluate the pattern of metastasis, response to chemotherapy, and survival in patients with metastatic synovial sarcoma. Results: Over a period of 4 years, 43 patients with metastatic synovial sarcoma were diagnosed with median age of 30 years. Nearly 70% of patients had lung metastasis, other site of metastasis were lymph node, bone, and liver. Thirty patients received chemotherapy with a combination of ifosfamide and doxorubicin. The overall response rate was 87% with median progression-free survival of 8 months. Patients with lung only metastasis had better survival compared with nonpulmonary metastatic site (18 months vs. 12 months). The median survival was 18 months. Conclusion: Metastatic synovial sarcoma is chemoresponsive tumor with lung being the most common metastatic site. Patients with lung only metastasis had a better outcome than nonpulmonary metastasis.

Summary The Choosing Wisely India campaign was an initiative that was established to identify low-value or potentially harmful practices that are relevant to the Indian cancer health-care system. We undertook a multidisciplinary framework-driven consensus process to identify a list of low-value or harmful cancer practices that are frequently undertaken in India. A task force convened by the National Cancer Grid of India included Indian representatives from surgical, medical, and radiation oncology. Each specialty had representation from the private and public sectors. The task force included two representatives from national patient and patient advocacy groups. Of the ten practices that were identified, four are completely new recommendations, and six are revisions or adaptations from previous Choosing Wisely USA and Canada lists. Recommendations in the final list pertain to diagnosis and treatment (five practices), palliative care (two practices), imaging (two practices), and system-level delivery of care (two practices). Implementation of this list and reporting of concordance with its recommendations will facilitate the delivery of high-quality, value-based cancer care in India.

Background: In MONALEESA-2, ribociclib plus letrozole showed improved progression-free survival compared with letrozole alone as first-line treatment for postmenopausal patients with hormone receptor (HR)-positive, HER2-negative, advanced breast cancer. MONALEESA-7 aimed to assess the efficacy and safety of ribociclib plus endocrine therapy in premenopausal women with advanced, HR-positive breast cancer. Methods: This phase 3, randomised, double-blind, placebo-controlled trial was done at 188 centres in 30 countries. Eligible patients were premenopausal women aged 18–59 years who had histologically or cytologically confirmed HR-positive, HER2-negative, advanced breast cancer; an Eastern Cooperative Oncology Group performance status of 0 or 1; measurable disease as per Response Evaluation Criteria in Solid Tumors version 1.1 criteria, or at least one predominantly lytic bone lesion; and had not received previous treatment with cyclin-dependent kinases 4 and 6 inhibitors. Endocrine therapy and chemotherapy in the adjuvant or neoadjuvant setting was permitted, as was up to one line of chemotherapy for advanced disease. Patients were randomly assigned (1:1) via interactive response technology to receive oral ribociclib (600 mg/day on a 3-weeks-on, 1-week-off schedule) or matching placebo with either oral tamoxifen (20 mg daily) or a non-steroidal aromatase inhibitor (letrozole 2·5 mg or anastrozole 1 mg, both oral, daily), all with goserelin (3·6 mg administered subcutaneously on day 1 of every 28-day cycle). Patients and investigators were masked to treatment assignment. Efficacy analyses were by intention to treat, and safety was assessed in all patients who received at least one dose of any study treatment. The primary endpoint was investigator-assessed progression-free survival. MONALEESA-7 is registered with ClinicalTrials.gov, NCT02278120 and is ongoing, but no longer enrolling patients. Findings: Between Dec 17, 2014, and Aug 1, 2016, 672 patients were randomly assigned: 335 to the ribociclib group and 337 to the placebo group. Per investigator's assessment, median progression-free survival was 23·8 months (95% CI 19·2–not reached) in the ribociclib group compared with 13·0 months (11·0–16·4) in the placebo group (hazard ratio 0·55, 95% CI 0·44–0·69; p

Background: Tumor lysis syndrome (TLS) is an oncological emergency associated with life-threatening metabolic abnormalities. Hyperuricemia is a feature of TLS and is treated with hydration, urine alkalinization, and allopurinol. Rasburicase lowers uric acid (UA) rapidly at the labeled dose of 0.15–0.2 mg/kg/day for 5 days. In a developing country like India where affordability is one major limitation to medical care, the use of rasburicase at the dose recommended by the US Food and Drug Administration (FDA) is not always possible. There is no convincing data suggesting the efficacy of a lower dose of rasburicase (1.5 mg or 3 mg) in the treatment of TLS. We conducted a retrospective study from January 2015 to June 2016 to assess the efficacy of a reduced-dose rasburicase in patients with TLS. Materials and Methods: All the patients with TLS were given rasburicase (single dose of 1.5 mg) on day 1 of chemotherapy. Serum UA, potassium, creatinine, and calcium levels were monitored every 24 h. All the patients who did not achieve normalization of UA with one dose of rasburicase were given another 1.5 mg of rasburicase. Results: Out of 90 patients, 54 patients (60%) had normalization of UA levels after 1.5 mg of rasburicase and 16 (18%) patients required 3 mg of rasburicase for bringing down the UA level to normal. The low serum UA levels were maintained even on the 3rd day of rasburicase. Rasburicase was well tolerated, and there was no death due to TLS. Thirty-one patients (64%) had normalization in the serum creatinine levels after rasburicase. Conclusion: We conclude that a low dose of rasburicase (1.5 mg or 3 mg) is cost effective in reducing serum UA (especially for low-risk and intermediate-risk TLS) and the higher dose as recommended by the US FDA is required only for patients with high-risk TLS.

Squamous cell carcinoma of the breast (SCCB) is a rare entity with limited data pertaining to the clinicopathological profile and treatment outcome. These tumors are characterized by rapid progression and have a poor outcome. The optimal therapy for SCCB has not yet been standardized. Most patients with SCCB are treated with the similar conventional chemotherapy regimens used in the ductal variant of breast cancer. This was an observational study of patients diagnosed with SCCB diagnosed from March 2013 to February 2015 at our institute. The medical records were reviewed and patients were contacted by telephone to study the clinicopathological profile and treatment outcome. We identified 5 (0.45%) patients of SCCB out of 1100 breast cancer patients treated in the department of medical oncology during this period. The median age at presentation was 48 years. All tumor specimens showed macroscopic findings of a cystic lesion and central necrosis. After a median follow-up of 32 months, 3 patients (60%) were alive, whereas 2 (40%) patients succumbed to disease progression after recurrence. SCCB is a rare subtype of breast cancer with no standard treatment approach. These are associated with poor prognosis and larger studies are needed to investigate different treatment options.

Objectives: The present study aimed to investigate the efficacy, toxicity, and impact of induction chemotherapy (IC) in technically unresectable T4a oral cavity squamous cell cancers (OSCCs). Materials and Methods: Patients diagnosed with technically unresectable locally advanced T4a OSCC from January 2013 and November 2016 at our center, who received 2–3 cycles of IC and then assessed for resectability, were reviewed retrospectively. Patients' profile, response rates and toxicity of IC, resectability status, and overall survival (OS) were evaluated. Statistical analyses were performed using SPSS version 17.0 for Windows (SPSS Inc., Chicago, IL, USA). Results: Totally 80 patients received IC, and of them 58 (72.5%) were males. Median age at diagnosis was 44 years (range, 34–62 years). All our patients received IC with doublet regimen. Majority of the patients had buccal mucosa cancers (73.8%), followed by gingivobuccal complex (21.2%) and oral tongue (5%) primaries. After IC, partial response was achieved in 17 (21.3%) patients, stable disease in 49 (61.3%) patients and disease progression was noted in 14 (17.4%) patients. Post-IC, resectability was achieved in 19 (23.8%) of 80 patients, but 4 of them did not undergo surgery due to logistic and personal reasons. The median OS of patients who underwent surgery followed by adjuvant local therapy (n = 15) was 16.9 months (95% CI: 15.2–19.8 months) and for those treated with nonsurgical local therapy (n = 65) was 8.8 months (95% CI: 6.8–10.6 months) (log-rank P = 0.000). Conclusions: IC had a manageable toxicity profile and achieved resectability in 23.8% of our patients with technically unresectable T4a OSCC. Patients underwent resection had a significantly better median OS than those who received nonsurgical local treatment.

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. World J Oncol. 2017;8(4):110-116 doi: https://doi.org/10.14740/wjon1054w

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Historically, a poor prognosis for metastatic disease has been reported with systemic chemotherapy. Significant advances have been made in the last decade, since the introduction of different tyrosine kinase inhibitors (TKIs). Unfortunately, even though the TKIs have been used for a long time, there are very few published data of the experience of TKI therapy in metastatic GIST from India. Materials and Methods: Patients diagnosed with metastatic GIST from January 2005 to October 2016 at our center, who received first-line therapy with imatinib 400 mg/day, were reviewed retrospectively. Patients' profile, response to treatment, toxicity of TKI therapy, time to progression, and survival were evaluated. Results: Of the 44 metastatic GIST patients, 23 (52.2%) were males. Median age at diagnosis was 48 years. The most common presenting symptom was an abdominal pain (52%), followed by weight loss (23%). Most frequently affected metastatic site was liver (57%), followed by peritoneum (16%), and lungs (4.5%). Metastases to both liver and peritoneum were found in 10 patients (22.5%). All patients were initially treated with imatinib at a dose of 400 mg/day. Disease stabilization was documented in 21 cases (48%), and 13 patients (29%) achieved a partial response. TKI therapy was well-tolerated in most cases. Median progression-free survival (PFS) was 26 months, and estimated median survival was 48 months. Patients with lung metastases have a significantly inferior median PFS and overall survival, in comparison to patients with other metastatic sites (P < 0.05). Conclusions: Imatinib therapy was well tolerated and induced a sustained clinical benefit in more than half of the patients with metastatic GIST. Lung metastases seemed to be a poor prognostic factor in this patient population.

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.

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

BACKGROUND: Recently published prospective clinical trials and two meta-analyses have shown that addition of induction chemotherapy (IC) to concurrent chemoradiation (CRT) could potentially improve outcomes in comparison to CRT alone, in locoregionally advanced nasopharyngeal carcinoma (LANPC). Although it remains unclear which is the best IC regimen to be offered and for how many cycles. Unfortunately, till date, there are no published data from India regarding the outcomes of various commonly used IC regimens before CRT, in LANPC. MATERIALS AND METHODS: Patients diagnosed with LANPC from January 2012 to December 2017, who received three cycles of IC before definitive CRT were reviewed retrospectively. Patients' profile, toxicity of IC, response rates, failure-free survival, and overall survival (OS) were evaluated. RESULTS: A total 34 patients with LANPC who received IC were reviewed. The median age at diagnosis was 36 years, and the majority were males (67.6%, n = 23). Nineteen patients received IC with paclitaxel plus cisplatin regimen (TP) and the remaining 15 patients received IC with docetaxel/paclitaxel plus cisplatin plus 5-FU regimen (TPF). The overall response rates after three cycles of TP and TPF IC were 68.4% and 80%, respectively, and the corresponding rates were 84.2%and 93.3%, respectively, 2 months after completion of CRT. At a median follow-up of 24 months, 2-year failure-free survival and OS for TP arm were 78.9% and 89.5%, and the corresponding rates for TPF arm were 86.7% and 93.3%, respectively. All Grade III–IV toxicities were numerically higher with triplet IC regimen in comparison to doublet regimen. CONCLUSION: In this retrospective analysis, there was no significant difference between taxane-based doublet and triplet IC regimens, in terms of survival outcomes, although Grade III–IV toxicities were numerically higher with triplet IC regimen. Clearly, these hypothesis-generating findings should be tested in a prospective randomized setting.

Patients diagnosed with chronic lymphocytic leukemia (CLL) are usually elderly and frequently have a number of comorbidities. Health-related quality of life (HRQoL) for these patients is of utmost importance and should be taken into consideration when assessing new treatment options. The combination of ofatumumab with chlorambucil has shown longer progression-free survival compared with chlorambucil alone. In this study, we aim to assess how this treatment combination affects patients' health-related quality of life and patient-reported symptoms.In this open-label phase III trial, patients with previously untreated CLL for whom fludarabine-based treatment was contra-indicated, were randomized 1:1 to receive oral chlorambucil (10 mg/mPatient-reported improvements from baseline in Global Health Status (GHS)/HRQoL scores and fatigue scores were recorded during treatment with both chlorambucil monotherapy and ofatumumab in combination with chlorambucil. There were no significant differences between the two treatment arms for GHS/HRQoL (p = 0.667) or fatigue (p = 0.103). Following treatment, numerical improvements to GHS/HRQoL and fatigue scores were reported, with no significant differences between the two treatment arms.Small but detectable improvements in patients' quality of life were reported as a result of treatment. The addition of ofatumumab to chlorambucil did not negatively impact HRQoL. Quality of life was maintained in the months following treatment.

Introduction: Febrile neutropenia (FN) is an oncological emergency. The choice of empiric therapy depends on the locally prevalent pathogens and their sensitivities, the sites of infection, and cost. The Infectious Diseases Society of America guidelines are being followed for the management of FN in India. Methods: This is a prospective observational study conducted at a tertiary care cancer centre from September 2012 to September 2014. Objectives: The objectives of this study were as follows: (1) To review the pattern of microbial flora, susceptibility pattern, and important clinical variables among bloodstream infections in febrile neutropenic patients with solid tumors and hematological malignancies. (2) As per the institutional protocol to periodically review the antibiotic policy and susceptibility pattern, and compare the findings with an earlier study done in our institute in 2010. This was a prospective study conducted from September 2012 to September 2014. Results: About 379 episodes of FN were documented among 300 patients. About 887 blood cultures were drawn. Of these, 137 (15%) isolates were cultured. Isolates having identical antibiograms obtained from a single patient during the same hospitalization were considered as one. Hence, 128 isolates were analyzed. About 74 (58%) cultures yielded Gram-negative bacilli, 51 (40%) were positive for Gram-positive cocci, and 3 (2%) grew fungi. Among Gram-negative organisms, Escherichia coli followed by Acinetobacter baumannii and Klebsiella pneumoniae accounted for 78% of the isolates. Among Gram-positive cocci, Staphylococcus species accounted for 84% of the isolates. We have noted a changing trend in the antibiotic sensitivity pattern over the years. Following the switch in empirical antibiotics, based on the results of the study done in 2010 (when the empirical antibiotics were ceftazidime + amikacin), the sensitivity to cefoperazone-sulbactam has plunged from about 80% to 60%%. Similar reduction in susceptibility was noted for piperacillin-tazobactam, imipenem, and meropenem. On the contrary, there was a marked increase in sensitivity to ceftazidime (50–76%). Based on these results, we have reverted to ceftazidime + amikacin as the empirical antibiotics. Conclusion: Every institute must have a regular revision of antibiotic policy based on periodic assessment of the clinical and microbiological profile in FN. This will combat antibiotic resistance.

Paclitaxel is widely used in the treatment of patients with metastatic breast cancer (MBC). Formulations of paclitaxel contain surfactants and solvents or albumin derived from human blood. The use of co-solvents such as polyoxyethylated castor oil is thought to contribute to toxicity profile and hypersensitivity reactions as well as leaching of plasticizers from polyvinyl chloride bags and infusion sets. Currently, nab-paclitaxel, an albumin-bound paclitaxel in nanometer range continues to be the preferred taxane formulation used in clinic. This study (CTRI/2010/091/001116) investigated the efficacy and tolerability of a polyoxyethylated castor oil- and albumin-free formulation of paclitaxel [paclitaxel injection concentrate for nanodispersion (PICN)] compared with nab-paclitaxel in women with refractory MBC. The current study was a multicenter, open-label, parallel-group, randomized, comparative phase II/III trial evaluating the efficacy and safety of PICN (260 mg/m(2) [n = 64] and 295 mg/m(2) [n = 58] every 3 weeks) compared with nab-paclitaxel (260 mg/m(2) every 3 weeks [n = 58]) in women 18 and 70 years old with confirmed MBC. Overall response rate (ORR) was assessed with imaging every 2 cycles. An independent analysis of radiologic data was performed for evaluable patients. Progression-free survival (PFS) was a secondary efficacy measure. Independent radiologist-assessed ORRs in the evaluable population of women aged ≥70 years were 35, 49, and 43 % in the PICN 260 mg/m(2), PICN 295 mg/m(2), and nab-paclitaxel 260 mg/m(2) arms, respectively. Median PFS in the evaluable population was 23, 35, and 34 weeks in the PICN 260 mg/m(2), PICN 295 mg/m(2), and nab-paclitaxel 260 mg/m(2) arms, respectively. Adverse events occurred in similar proportions of patients across treatment arms. Hypersensitivity reactions were not frequently observed with the clinical use of PICN across the treatment cohorts. In women with metastatic breast cancer, PICN at 260 and 295 mg/m(2) every 3 weeks was effective and well tolerated and showed similar tolerability compared with nab-paclitaxel 260 mg/m(2) every 3 weeks. Statistically, significant differences were not observed in the PICN and nab-paclitaxel treatment arms for radiologist-assessed ORR or median PFS. The novel paclitaxel formulation, PICN, offers apart from efficacy, potential safety advantage of decreased use of corticosteroid pretreatment and the absence of the risk of transmission of blood product-borne disease.

Introduction: Prolonged treatment, frequent administration of chemotherapy, antibiotics and blood products in cancer patients requires long term venous access. Central venous catheters (CVC) inserted into the subclavian vein or internal jugular vein, peripherally inserted central venous catheters (PICC) and chemoport (CP) are the commonly used central venous access devices (CVAD). Aim: This study was envisaged to review our experience of CVADs over a one year period and analyze the outcome with regard to catheter life, reasons for removal, complications, patient satisfaction and cost comparison between the CVAD types in the Indian setting. Settings and Design: This was a prospective, observational study carried out in a tertiary care cancer institute. Materials and Methods: 180 CVADs placed in patients with hematological malignancies and solid tumors from January 2014 to December 2014 were included. Statistical Analysis Used: Data was analyzed using descriptive statistics, Mann Whitney U test. P

Background.Acute promyelocytic leukemia is characterized by t(15;17). This leads to the formation of PML/RARαwhich blocks the differentiation of blasts at the stage of promyelocytes. This is reversed by all-trans-retinoic acid (ATRA), a vitamin A derivative. Acute myocardial ischemia is a rare side effect of ATRA.Case Report.We report a case of acute coronary syndrome manifesting as an adverse effect of ATRA in a lady with APL who had no other risk factors for cardiovascular disease.Conclusions.We emphasize the need for high index of suspicion for the diagnosis of this entity. In the light of this case, the rare instances of ATRA associated acute myocardial ischemia recorded in the literature and the options available for treatment of acute promyelocytic leukemia sans ATRA have been reviewed.

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.

Introduction: Plasmablastic lymphoma (PBL) is a rare lymphoma associated with immunosuppression. It is strongly associated with immunosuppression (human immunodeficiency virus [HIV]) and often occurs within the oral cavity. PBL is also seen in patients receiving immunosuppressive therapy; however, despite its predisposition for the immunocompromised patients, PBL has been diagnosed in immunocompetent patients. Aim: This study aims to prognostic factors and outcome of PBL in immunocompromised and in immunocompetent patients. Materials and Methods: We conducted a retrospective study at our institute from the year 2008 to 2015. Results: A total of 13 patients (8 males and 5 females) with PBL were identified. Eight patients (61.5%) had extraoral PBL (median age 30.2 years) and 5 patients (38.5%) had oral PBL (median age 44 years). Most common extraoral site was gastrointestinal tract. Eight (61.5%) out of 13 patients were HIV positive. More than 50% of patients had Ann Arbor Stage III or IV. All the cases were CD20 negative and CD138 positive. Seven out of 13 patients had Ki-67 more than 80%. Nine patients received cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Three patients were on best supportive care due to poor performance status (PS). One patient received intensive chemotherapy with CODOX-M/IVAC. The median overall survival was 9 months in HIV-positive patients and 6 months in HIV-negative patients. The prognosis was worse in patients with Ki-67 of >80%. Statistical Analysis: Survival curves were generated using the Kaplan–Meier method and analyzed using log-rank test and Fisher's t-test. Conclusion: The present study confirms that PBL in both HIV-positive and in HIV-negative patients has an overall unfavorable outcome. The most important prognostic factors are stage, ki-67, and the Eastern Cooperative Oncology Group PS of the patient at the time of presentation.

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

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

Background Acute erythroid leukaemia (AEL) is a rare subtype of acute myeloid leukaemia (AML), constituting

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.

Chronic lymphocytic leukemia (CLL) is an incurable disease. Quality of life during treatment and periods of subsequent remission is therefore vital. Health-related quality of life (HRQoL) was compared in relapsed CLL during and after treatment with ofatumumab combined with fludarabine and cyclophosphamide versus fludarabine and cyclophosphamide alone. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 v3 and QLQ-CLL16 were used to assess HRQoL in this open-label, phase 3 study. Improvements in prespecified domains of patient-reported outcomes (Global Health Status [GHS]/HRQoL and B symptom scores) were recorded in both treatment arms after three cycles and were sustained after 18 months of follow-up. The two treatment arms were not significantly different at the nominal 0.05 level for GHS/HRQoL (p = .7278) or B symptoms (p = .5968). Small improvements in quality of life were maintained after therapy. The addition of ofatumumab was without any adverse impact on HRQoL (NC...

In this multicenter, open-label, phase III study, patients with relapsed chronic lymphocytic leukemia (CLL) were randomized (1:1) to receive ofatumumab plus fludarabine and cyclophosphamide (OFA + FC) or FC alone; the primary endpoint being progression-free survival (PFS) assessed by an independent review committee (IRC). Between March 2009 and January 2012, 365 patients were randomized (OFA + FC: n = 183; FC: n = 182). Median IRC-assessed PFS was 28.9 months with OFA + FC versus 18.8 months with FC (hazard ratio = 0.67; 95% confidence interval, 0.51–0.88; p = .0032). Grade ≥3 adverse events (≤60 days after last dose) were reported in 134 (74%) OFA + FC-treated patients compared with 123 (69%) FC-treated patients. Of these, neutropenia was the most common (89 [49%] vs. 64 [36%]). OFA + FC improved PFS with manageable safety for patients with relapsed CLL compared with FC alone, thus providing an alternative treatment option for patients with relapsed CLL. Trial registration: www.clinicaltrials.gov...

Cancer-associated thrombotic microangiopathy refers to a group of disorders characterised by microvascular thrombosis, thrombocytopenia, and ischaemic end-organ damage. Haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura are the two major subtypes. It can be a manifestation of the malignancy itself or a complication of its therapy. The addition of several new drugs to the therapeutic armamentarium of cancer has brought to light several novel causative factors of this hitherto uncommon complication. This review covers the aetiology, pathogenesis, clinical manifestations, complications, and the management of cancer-associated thrombotic microangiopathy. Careful review of the patient's medical records coupled with the correlation of clinical findings and laboratory reports can help clinch the diagnosis and institute appropriate treatment on time.

Summary Background Optimal management of patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response remains undetermined. This study aimed to investigate the safety and efficacy of switching to nilotinib vs imatinib dose escalation for patients with suboptimal cytogenetic response on imatinib. Methods We did a phase 3, open-label, randomised trial in patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response to imatinib according to the 2009 European LeukemiaNet criteria, in Latin America, Europe, and Asia (59 hospitals and care centres in 12 countries). Eligible patients were aged 18 years or older with Philadelphia chromosome-positive chronic myeloid leukaemia in chronic phase and Eastern Cooperative Oncology Group performance status of 0–2. Before enrolment, all patients had received 3–18 months of imatinib 400 mg once daily and had a suboptimal cytogenetic response according to 2009 ELN recommendations, established through bone marrow cytogenetics. By use of an interactive response technology using fixed blocks, we randomly assigned patients (1:1) to switch to nilotinib 400 mg twice per day or an escalation of imatinib dose to 600 mg once per day (block size of 4). Investigators and participants were not blinded to study treatment. Crossover was allowed for loss of response or intolerance at any time, or for patients with no complete cytogenetic response at 6 months. The primary endpoint was complete cytogenetic response at 6 months in the intention-to-treat population. Efficacy endpoints were based on the intention-to-treat population, with all patients assessed according to the treatment group to which they were randomised (regardless of crossover); the effect of crossover was assessed in post-hoc analyses, in which responses achieved after crossover were excluded. We present the final results at 24 months' follow-up. This study is registered with ClinicalTrials.gov (NCT00802841). Findings Between July 7, 2009, and Aug 29, 2012, we enrolled 191 patients. 96 patients were randomly assigned to nilotinib and 95 patients were randomly assigned to imatinib. Complete cytogenetic response at 6 months was achieved by 48 of 96 patients in the nilotinib group (50%, 95·18% CI 40–61) and 40 of 95 in the imatinib group (42%, 32–53%; difference 7·9% in favour of nilotinib; 95% CI −6·2 to 22·0, p=0·31). Excluding responses achieved after crossover, 48 (50%) of 96 patients in the nilotinib group and 34 (36%) of 95 patients in the imatinib group achieved complete cytogenic response at 6 months (nominal p=0·058). Grade 3–4 non-haematological adverse events occurring in more than one patient were headache (nilotinib group, n=2 [2%, including 1 after crossover to imatinib]; imatinib group, n=1 [1%]), blast cell crisis (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%]), and QT prolongation (nilotinib group, n=1 [1%]; imatinib group, n=1 [1%, after crossover to nilotinib]). Serious adverse events on assigned treatment were reported in 11 (11%) of 96 patients in the nilotinib group and nine (10%) of 93 patients in the imatinib group. Seven (7%) of 96 patients died in the nilotinib group and five (5%) of 93 patients died in the imatinib group; no deaths were treatment-related. Interpretation While longer-term analyses are needed to establish whether the clinical benefits observed with switching to nilotinib are associated with improved long-term survival outcomes, our results suggest that patients with suboptimal cytogenetic response are more likely to achieve improved cytogenetic and molecular responses with switching to nilotinib than with imatinib dose escalation, although the difference was not statistically significant when responses achieved after crossover were included. Funding Novartis Pharmaceuticals.

Sokal index was developed in the pre-imatinib era to predict and prognosticate the outcome of Chronic myeloid leukemia (CML) patients. In the Imatinib era, a new scoring system called EUTOS scoring system has been validated as a predictive marker in CML. The scores have shown variable correlation with complete cytogenetic response (CCyR) and major molecular response (MMR). To assess the performance of Sokal score and EUTOS score as a predictive marker for CCyR and MMR for newly diagnosed CML-CP patients treated with TKIs. 273 patients with newly diagnosed CML were included in the study. They were treated with upfront imatinib. They were followed up for a median period of 3 years. Cytogenetic and Molecular response to the treatment were monitored regularly. Out of 273 patients, 174 patients (63 %) were having low EUTOS score and 99 (37 %) were having high EUTOS score. Patients with low, intermediate and high sokal scores were 237 (86.8 %), 28 (10.3 %) and 8 (2.9 %) respectively. 122 patients with low EUTOS score achieved CCyR within 18 months compared to 42 patients with high EUTOS score (p = 0.000).113 patients with low EUTOS score achieved MMR in 18 months compared to 33 patients with high EUTOS score (p = 0.000). 148, 14, 2 patients with low, intermediate and high Sokal score respectively have achieved CCyR in 18 months (p = 0.054). 133, 11, 2 patients with low intermediate and high sokal score respectively have achieved MMR in 18 months.(p = 0.06). EUTOS is better than Sokal score in predicting the outcome of patients of CML treated with imatinib.

INTRODUCTION: Multiple myeloma (MM) is a plasma cell dyscrasias and an incurable clonal B-cell malignancy, with an annual incidence of 1% of all malignancies. The mainstay of treatment of myeloma is induction treatment followed by consolidation with autologous stem cell transplant (ASCT). However, still in a developing country like India where affordability is a major hurdle for health care, a number of MM patients are not able to undergo ASCT. AIM: To study the epidemiological features and outcome of MM patients treated in a limited resource setting. MATERIALS AND METHODS: We conducted a retrospective study at our institute to identify patients diagnosed as MM from 2005 to 2016. We studied the epidemiological profile and the outcome of the treatment in terms of response rates and overall survival. STATISTICAL ANALYSIS: Survival analysis was performed using Kaplan–Meier curve. RESULTS: Median age at diagnosis is 54 years (range: 39–85 years). IgG myeloma was the most common type seen in 72% of patients. The International Staging System (ISS) was ISS I (31%), ISS II (30%), and ISS III (39%). The median duration of treatment for thalidomide + dexamethasone (TD) and bortezomib + TD (VTD) was 9 and 7 months, respectively. Median survival for the TD versus VTD regimen (in a nontransplant setting) for the ISS I, ISS II, and ISS III groups was 49 and 55 months (P = 0.056), 42 and 48 months (P < 0.05), 21 and 27 months (P < 0.05), respectively. CONCLUSION: Proteasome inhibitors significantly improved the median survival for patients with MM (ISS II and ISS III) treated in a limited resource setting.

Introduction: Bone metastasis is a rare site of metastasis, seen in only 3.7–11% of clinical cases. Isolated bone involvement has been reported very rarely in literature. Moreover, the patients who have bone metastasis at presentation are even rare. Objectives: To discuss the demographic characteristics, carcinoembryonic antigen (CEA) levels, pattern of bone involvement, and their correlation with survival in patients of colorectal cancer that have bone metastasis at the time of presentation. Materials and Methods: Retrospectively, tumor registry was analyzed for the cases of colorectal cancer presenting with bone metastasis between 2008 and 2013. Survival curves were generated by Kaplan–Meier method and analyzed using the log-rank test. Results: Ten such patients were identified (male:female = 7:3) of the total 410 patients. Median age was 41 years (22–50 years). All patients were < 50 years of age. Median CEA level was 147.5 (45–840). Three patients had bone-only metastasis. Most common metastatic site involved was liver (six patients) and lungs (three patients). The most common sites of bone metastasis were vertebra and pelvis (4 each). Chemotherapy was given in seven patients. Median overall survival was 5.5 months (2–36 months). It was higher in males, in those with bone-only involvement and those without liver involvement. Vertebral involvement, pelvic involvement, CEA levels, and chemotherapy did not show any significant survival implication. Conclusions: In this study, the patients of colorectal cancer presenting with bone metastasis were of male sex and younger age. The factors that were associated with reduced survival were extraosseous and liver involvement.

Background: Malignant infantile osteopetrosis (MIOP) is an autosomal recessive disorder which is characterized by densely sclerotic bone due to defective function of osteoclasts. Overgrowth of bone results in nerve compression and reduction of marrow spaces. It may be complicated by rickets. The main genetic causes are the mutations in the TCIRG1 and CLCN7 genes. Stem cell transplantation offers the only hope for cure. Early diagnosis is of prime importance. Case Presentation: We report a four month old female infant, who was diagnosed to have MIOP while being evaluated for raised total count, thrombocytopenia, hepatosplenomegaly and optic atrophy. An infantogram helped us clinch the diagnosis as she had most of the radiological signs that have been described. She was also found to have co-existent rickets. Mutation analysis and hematopoietic stem cell transplantation were deferred by her parents due to financial constraints. Conclusion: MIOP should be kept in mind when the patient presents with hematological abnormalities such as anemia, thrombocytopenia and leukemoid reaction along with hepatosplenomegaly and optic atrophy. Our case is worthy of mention, because a high index of suspicion and meticulous interpretation of the infantogram helped us arrive at the diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health burden and the seventh most common cause of cancer-related death in India. Patients with advanced unresectable HCC have a poor prognosis with a reported median survival of only 2–3 months with the best supportive care (BSC). Sorafenib is the only drug that has demonstrated a survival benefit over BSC in advanced HCC. Unfortunately, even though it has been used for a long time, there are very few published data regarding the experience of sorafenib therapy in advanced HCC from India. MATERIALS AND METHODS: Patients diagnosed with advanced HCC from January 2012 to July 2017 at our center were reviewed retrospectively. Patients' profile, time to progression, survival, and toxicity of sorafenib therapy were evaluated. RESULTS: Of the 48 advanced patients with HCC, 35 (72.9%) were male. The median age at diagnosis was 52 years. The most common presenting symptom was abdominal pain (77%, n = 37), followed by abdominal distension (37.5%, n = 18), loss of appetite and/or weight (33.3%, n = 16), and jaundice (16.7%, n = 8). Hepatitis B virus infection was documented in 37 patients (77%), whereas 4 patients had hepatitis C virus infection. Patients were treated with standard dose sorafenib (n = 30), BSC alone (n = 14), or transarterial chemoembolization followed by sorafenib (n = 4). Sorafenib therapy was well-tolerated in most cases. The median progression-free survival with upfront sorafenib was 4.3 months. The median overall survival (OS) of the patients who received upfront sorafenib was significantly better than those treated with BSC alone (5.9 vs 3.0 months; log-rank P= 0.00). CONCLUSION: Sorafenib therapy was well-tolerated and provided about 3 months longer median OS in our patients with advanced HCC than those treated with BSC alone.

Introduction: Ph+ AML is a well-recognized , but rare entity that poses challenges to clinicians to differentiate it from Chronic myeloid leukemia in blast crisis. Objective: Our aim was to study the clinical profile, treatment and outcomes of patients with Ph+ AML at our centre. Materials and Methods: Four cases of Ph+ AML entered in the hospital registry between 2013 and 2015 were identified and analysed. Results: The median age was 46 years with equal sex preponderance. The duration of presenting complaints was