Diving deep for the needle in the haystack: An outbreak investigation of Burkholderia cenocepacia bacteremia.

In an Indian oncology setting, between August and December 2021, 56 patients, developed Burkholderia cenocepacia bacteremia. An investigation revealed a contaminated batch of the antiemetic drug palonosetron. The outbreak was terminated by withdrawing the culprit batch and the findings were reported promptly to regulatory authorities.

Flow Cytometry Based MRD and Its Impact on Survival Outcome in Children and Young Adults with ALL: A Prospective Study from a Tertiary Cancer Centre in Southern India.

Presence of minimal residual disease (MRD) following induction chemotherapy is a well-recognized risk factor to predict relapse in acute lymphoblastic leukemia (ALL). There is paucity of data on MRD and outcome in ALL from India. We share our experience in establishing a flow cytometry-based MRD assay for ALL with emphasis on determination of the number of patients who had MRD on day 35 of induction therapy and its correlation with outcome and other prognostic factors. We prospectively studied MRD in patients with ALL less than 25 years who achieved morphological complete remission with induction therapy. The initial series consisted of 104 patients with ALL. Ninety-two patients had bone marrow samples collected on day 35 of remission induction chemotherapy that was adequate for MRD. Strategy of monitoring MRD was based on flow cytometry using six color staining according the leukemia associated immunophenotype found at diagnosis. Data analysis was done using Fisher exact test. The median age was 8.5 years (range 0.9-22 years). Thirty-seven out of ninety-two patients (40.2%) had MRD at end of induction. MRD on day 35 was between 0.01 and 0.1% in 18.9% of patients, between 0.1 and 1% in 59.5% and more than 1% in 21.6% patients. Among the patients who had MRD, 16.7% had favourable cytogenetics, 60% had intermediate and 13.3% had high-risk cytogenetics. The presence or absence of residual leukemia by flow cytometry at day 35 was not significantly related to age (p = 1.0), male gender (p = 0.08) hyperleukocytosis (p = 0.25) or day 8 blast clearance (p = 0.21). However, T cell phenotype (p < 0.001) was significantly associated with MRD. The 5-year event free survival (EFS) for patients who had MRD versus those who did not was 69% and 61.1% respectively (p = 0.41). The 5-year overall survival (OS) for patients who had MRD versus those who did not was 72.5% and 61.1% respectively (p = 0.33). Flow cytometric techniques can be applied to monitor MRD in patients of ALL undergoing induction therapy. Our results suggest MRD correlates with certain known prognostic factors. Though the EFS and OS was lower in MRD positive patients, the results were not statistically significant probably because of the small sample size.

Novel formulations of docetaxel, paclitaxel and doxorubicin in the management of metastatic breast cancer.

The management of breast cancer with advanced disease or metastasis is a common problem in India and other countries. A panel of 13 oncology experts deliberated on the sidelines of the 35th Indian Cooperative Oncology Network Conference held in Mumbai to formulate an expert opinion recommendation on the novel drug delivery system (NDDS) formulations in the treatment of metastatic breast cancer (MBC). The survey comprised of 39 questions related to limitations of conventional formulations and therapeutic positioning of NDDS formulations of docetaxel, paclitaxel and doxorubicin in the management of MBC. The experts used data from published literature and their practical experience to provide expert opinion and recommendations for use by the community oncologists. The experts opined that the newer NDDS formulations should provide a significant efficacy advantage in terms of overall survival and progression-free survival, or demonstrate better tolerability when compared with conventional formulations. The newer NDDS formulations of taxanes should be considered in special circumstances such as diabetes, in patients who have had hypersensitivity reactions and in cases where steroids need to be avoided. The novel formulations of doxorubicin should be used in the elderly and in patients with borderline cardiac function.

Outcomes in Lung Cancer: 9-Year Experience From a Tertiary Cancer Center in India.

PURPOSE: Lung cancer is the most common cause of cancer mortality in the world. There are limited studies on survival outcomes of lung cancer in developing countries such as India. This study analyzed the outcomes of patients with lung cancer who underwent treatment at Cancer Institute (WIA), Chennai, India, between 2006 and 2015 to determine survival outcomes and identify prognostic factors. PATIENTS AND METHODS: In all, 678 patients with lung cancer underwent treatment. Median age was 58 years, and 91% of patients had non-small-cell lung cancer (NSCLC). Testing for epidermal growth factor receptor mutation was performed in 132 of 347 patients and 61 (46%) were positive. RESULTS: Median progression-free survival was 6.9 months and overall survival (OS) was 7.6 months for patients with NSCLC. Median progression-free survival was 6 months and OS was 7.2 months for patients with small-cell lung cancer. On multivariable analysis, the factors found to be significantly associated with inferior OS in NSCLC included nonadenocarcinoma histology, performance status more than 2, and stage. In small-cell lung cancer, younger age and earlier stage at presentation showed significantly better survival. CONCLUSION: Our study highlights the challenges faced in treating lung cancer in India. Although median survival in advanced-stage lung cancer is still poor, strategies such as personalized medicine and use of second-line and maintenance chemotherapy may significantly improve the survival in patients with advanced-stage lung cancer in developing countries.

Predictors of Chemotherapy Related Toxicities in Elderly Lymphoma Patients: Experience from a Tertiary Cancer Centre.

Identification of baseline parameters that predict chemotherapy related morbidities in elderly lymphoma patients can help in tailoring treatment. However, there is a paucity of tools to predict the risk of chemotherapy related toxicity in elderly lymphoma patients from India. We retrospectively analyzed 203 lymphoma patients more than 60 years of age for predictors of grade III or higher haematological and non-haematological toxicity due to chemotherapy. Eighty-five (42%) and seventy-one (35%) lymphoma patients developed grade III or IV haematological and non-haematological toxicities respectively. On multivariate analysis baseline absolute lymphocyte counts (ALC) less than 1300/µl, chemotherapy with anthracyclines and presence of two co-morbid conditions were significant in predicting serious haematological toxicities. For non-haematological toxicities baseline ALT levels more than 40 U/l was the only significant factor. This is the first report from India on the study of factors predicting serious chemotherapy related adverse effects in elderly lymphoma patients. Patients with low ALC, elevated ALT, multiple co-morbidities and receiving anthracyclines should be closely monitored for chemotherapy related toxicities.

Differential Toxicities of Tyrosine Kinase Inhibitors in the Management of Metastatic Lung Cancer.

INTRODUCTION: Erlotinib and gefitinib are the most commonly used epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of EGFR mutant nonsmall cell lung cancer (NSCLC). Both erlotinib and gefitinib have shown equal efficacy in terms of response rates and overall survival. Hence, their toxicity profile becomes the most important determining factor in choosing these agents when treating EGFR mutant NSCLC. In this study, we compared the toxicity profile of erlotinib and gefitinib among an Indian subset of lung cancer patients. MATERIALS AND METHODS: In this prospective nonrandomized study, 85 patients of South Indian origin with NSCLC were tested for EGFR mutation status, and EGFR mutant patients were started on either erlotinib or gefitinib. They were periodically monitored for drug toxicities. RESULTS: Out of the 85 patients tested, 34 patients were positive for EGFR mutation. Eleven of them were started on erlotinib and 23 were started on gefitinib. The most common side effect of TKIs was skin rash. Nine out of the 11 patients started on erlotinib and 7 of the 23 patients started on gefitinib had skin rash. Grade 3 and 4 skin rash was significantly more among patients treated with erlotinib which resulted in treatment delays. Other side effects of TKIs such as diarrhea and deranged liver functions were similar among the both subsets of patients. CONCLUSION: Skin toxicity is the major and serious side effect with erlotinib among Indian patients with EGFR mutant lung cancer. This resulted in significant treatment delay, which might adversely affect the overall survival of patients. Gefitinib was better tolerated and had a safer toxicity profile compared to erlotinib in Indian patients.

Acute Myeloid Leukemia in Children: Experience from Tertiary Cancer Centre in India.

There is paucity of data in pediatric Acute Myeloid Leukemia (AML) from developing countries. We analyzed the outcomes of 65 consecutive patients with pediatric AML treated at our centre from January-2008 to May-2013. The median event free survival (EFS) and overall survival (OS) were 12.6 and 14.6 months respectively. Patients with good-risk cytogenetics had a better EFS (p = 0.004) and OS (p = 0.01). Overall, these results are not comparable to that observed in other centres globally and leaves scope for further improvement. This includes implementing allogeneic bone marrow transplantation as a treatment for all children with high-risk AML.

Comprehensive Evaluation of Adherence to Therapy, Its Associations, and Its Implications in Patients With Chronic Myeloid Leukemia Receiving Imatinib.

BACKGROUND: Adherence to oral therapy over a long period is important for optimal outcomes in chronic myeloid leukemia (CML). METHODS: Patients in the chronic phase of CML (taking imatinib for ≥ 6 months) were assessed by the 8-item Morisky Medication Adherence Scale and European Organisation for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire (C30 and CML 24). Patients were classified as adherent (score 8) and nonadherent (score ≤ 7) as per the 8-item Morisky Medication Adherence Scale. RESULTS: Among 221 patients (male to female ratio = 133:88; median age, 39 (18-65) years; median duration of imatinib, 4 years), the nonadherence rate was 55% (N = 122/221). None of the demographic parameters, including occupation, education status, income, and availability of caregiver, were associated with nonadherence. QoL scores, especially the symptom scores associated with side effects of imatinib, significantly differed between adherent and nonadherent patients. Multivariate analysis revealed global health status as the sole predictor of adherent behavior (odds ratio, 0.978; 95% confidence interval, 0.963-0.994; P = .007). A higher proportion of adherent patients achieved deeper molecular responses. Low QoL was associated with nonadherence to imatinib in patients with CML. CONCLUSIONS: It is likely that increased long-term symptom burden due to side effects of imatinib could contribute to nonadherence. Interventions targeting individual components of QoL may improve adherence and outcomes in CML.

Voriconazole is a safe and effective anti-fungal prophylactic agent during induction therapy of acute myeloid leukemia.

BACKGROUND: Antifungal prophylaxis (AFP) reduces the incidence of invasive fungal infections (IFIs) during induction therapy of acute myeloid leukemia (AML). Posaconazole is considered the standard of care. Voriconazole, a generic cheaper alternative is a newer generation azole with broad anti-fungal activity. There is limited data on the use of voriconazole as a prophylactic drug. MATERIALS AND METHODS: A single-center, prospective study was performed during which patients with AML undergoing induction chemotherapy received voriconazole as AFP (April 2012 to February 2014). Outcomes were compared with historical patients who received fluconazole as AFP (January 2011-March 2012, n = 66). RESULTS: Seventy-five patients with AML (median age: 17 years [range: 1-75]; male:female 1.6:1) received voriconazole as AFP. The incidence of proven/probable/possible (ppp) IFI was 6.6% (5/75). Voriconazole and fluconazole cohorts were well-matched with respect to baseline characteristics. Voriconazole (when compared to fluconazole) reduced the incidence of pppIFI (5/75, 6.6% vs. 19/66, 29%; P < 0.001), need to start therapeutic (empiric + pppIFI) antifungals (26/75, 34% vs. 51/66, 48%; P < 0.001) and delayed the start of therapeutic antifungals in those who needed it (day 16 vs. day 10; P < 0.001). Mortality due to IFI was also reduced with the use of voriconazole (1/75, 1.3% vs. 6/66, 9%; P = 0.0507), but this was not significant. Three patients discontinued voriconazole due to side-effects. CONCLUSION: Voriconazole is an effective and safe oral agent for IFI prophylaxis during induction therapy of AML. Availability of generic equivalents makes this a more economical alternative to posaconazole.

Acute lymphoblastic leukemia: A single center experience with Berlin, Frankfurt, and Munster-95 protocol.

BACKGROUND: There is a paucity of data on the outcome following the treatment for acute lymphoblastic leukemia (ALL) from developing countries. MATERIALS AND METHODS: Two hundred and thirty-eight consecutive patients with ALL <30 years of age diagnosed between January 2005 and December 2011 were analyzed retrospectively. Patients were treated modified Berlin, Frankfurt, and Munster 95 protocol. Event-free survival (EFS) was calculated using Kaplan-Meier survival analysis and variables were compared using log-rank test. RESULTS: The EFS was 63.4% at a median follow-up was 32.7 months. On univariate analysis National Cancer Institute (NCI) risk stratification, sex, white blood cell count, day 8 blast clearance, and income were significantly associated with EFS. However, on multivariate analysis only female sex (P = 0.01) and day 8 blast clearance (P = 0.006) were significantly associated with EFS. Seventy-four of 238 (31%) patients had recurrent leukemia. The common sites of relapse were bone marrow in 55/74 (75%) patients and central nervous system in 11/74 (20%) patients. CONCLUSION: Compared to western data, there was an increased proportion of NCI high-risk patients and T-cell immunophenotype in our study. There has been an improvement in outcome of patients with ALL at our center over the last 2 decades. Female sex and clearance of blast in peripheral blood by day 8 of induction was associated with better EFS.

Treatment of chronic phase chronic myeloid leukemia with imatinib.

OBJECTIVE: To report outcomes of Chronic Myeloid Leukemia (CML) treated with upfront imatinib. METHODS: Outcomes of children (≤18 y) with chronic phase CML (CML-CP) treated with imatinib over a 5 y (2003-2008) period were retrospectively analyzed to quantify responses, progression free survival (PFS) and overall survival (OS). RESULTS: Thirty-one patients (age range: 6-18 y) received therapy with imatinib 260-300 mg/m(2). Thirty (97 %) achieved complete hematological response at a median of 2 mo from start of treatment. Major and complete cytogenetic response rates at 2 y were 82 % and 70 % respectively. After a median follow up of 49.2 mo the 5 year PFS and OS were 68 % and 76 % respectively. Out of the 16 patients with documented Complete Cytogenetic Response (CCR) at 2 y, none progressed during subsequent follow up. There were no serious toxicities. Most patients who progressed, died of the disease. CONCLUSIONS: Imatinib is a reasonable first line therapy in pediatric CML-CP, which is effective and well tolerated. Outcomes are comparable to those reported from the West. Availability of second line agents and increased access to stem cell transplantation could further improve outcomes.

Immediate treatment effects of high-dose methotrexate and cranial irradiation on neuropsychological functions of children treated for acute lymphoblastic leukemia at a regional cancer center.

CONTEXT: Overall cure rates for pediatric acute lymphoblastic leukemia (ALL) have improved; however, the neuropsychological sequelae of ALL treatment have not been adequately documented in India. AIMS: The present study assesses the immediate effects of ALL treatment on neuropsychological functioning, at the Regional Cancer Center in Chennai, South India. MATERIALS AND METHODS: Newly diagnosed with ALL patients (n = 24) (aged 6-15 years; 13M:11F) registered between March 2008 and February 2009 were included. Patients who had received high-dose methotrexate (HD-MTX) and cranial radiotherapy (CRT) as part of their treatment were enrolled for the study. Neurocognitive assessments were done to assess various functions such as performance intelligence, visuo-perception, visuo-spatial, perceptual organization, processing speed, planning, working memory, and immediate verbal memory (IVM) (Malin's intelligence scale); verbal fluency (ideation fluency test) and verbal attention (vigilance test). Three assessments were done during induction (baseline), after re-induction phase (second) and during the maintenance phase (third). RESULTS: The patients performed significantly worse in the third assessment (mean duration from diagnosis 17.48 months) on performance intelligence quotient (PIQ), visuo-perception, visuo-spatial, processing speed, planning, IVM, verbal attention, and verbal fluency (P < 0.05), there were no significant changes observed in visuo-perceptual organization and working memory (P > 0.05). Significant difference was observed between age groups 6 and 10 (41.7%) and 11-15 years (58.3%) in perceptual organization, verbal fluency, and verbal attention (P < 0.05) and no gender difference was observed across the three assessments (P > 0.05). CONCLUSIONS: Combining HD MTX and CRT had an immediate effect on neuropsychological sequelae among the children with ALL, however, long-term evaluation is recommended to study the long-term effects.

Late effects of treatment in survivors of childhood cancer from a tertiary cancer center in South India.

BACKGROUND: Improved survival after childhood cancer is attributed to intensive, aggressive therapy, adverse sequelae of which can manifest months to years after completion of treatment. There is little information about the late adverse effects of both childhood cancer and its therapy in survivors in India. AIM: To determine the long-term sequelae associated with therapy in childhood cancer survivors attending a tertiary cancer center in India. MATERIALS AND METHODS: We studied 155 consecutive survivors of childhood cancer who were ≤14 years at the time of diagnosis and had completed 3 years of follow-up. The study included a complete history and clinical examination, with specific investigations to detect organ toxicity. Quality of life (QOL) was assessed from responses to a standardized questionnaire. Neurocognitive assessment was carried out in 20 survivors with an adaptation of the revised Wechsler adult intelligence scale for adults and the Malins intelligence scale for children. RESULTS: The late effects included impaired fertility in 38 patients (24.5%), impaired growth pattern in 7 (4.5%), endocrine dysfunction in 7 (4.5%) and second malignancy in 2 (1.2%). Three of the 20 patients assessed had severe neurocognitive impairment. A high QOL was reported by 60% of survivors and an "average" QOL by 38%. CONCLUSION: Our study showed that most survivors had a good QOL and our results will help clinicians to better monitor childhood cancer survivors in countries with limited resources.

Spontaneous regression of primary progressive Hodgkin's lymphoma in a pediatric patient: a case report and review of literature.

Spontaneous regression of malignancies is a very rare phenomenon. Our research of existing literature yielded only 16 cases of Hodgkin's lymphoma which regressed spontaneously. The outcome of primary progressive Hodgkin's lymphoma is poor even with salvage chemotherapy and autologous bone marrow transplantation. Here we present a case of primary progressive Hodgkin's lymphoma, which regressed spontaneously after failure of salvage chemotherapy. To our knowledge, this is the first case report of primary progressive Hodgkin's lymphoma undergoing spontaneous regression.

Complete clinical response to neoadjuvant chemoradiation in rectal cancers: can surgery be avoided?

BACKGROUND/AIMS: Neoadjuvant chemoradiation for rectal cancers may result in complete clinical response (cCR) in some patients. The aim of this study was to analyze the long-term outcomes of such patients in a tertiary cancer center. METHODOLOGY: Patients with rectal cancer who had a cCR to neoadjuvant chemoradiation were divided into two groups: Group A (n=23) did not undergo surgery, and Group B (n=10) underwent elective surgery. The recurrence patterns and survival outcomes were compared between the two groups. RESULTS: After a median follow-up of 72 months (range 12-180), seven patients (30%) in Group A developed an isolated local recurrence. In Group B, after a median follow-up of 37 months (range 12-180) there were no local recurrences. The median disease-free and overall survival was 36 months (range 6-168) and 66 months (range 12-180) in Group A and 36 months (range 12-180) and 37 months (range 18-180) in Group B respectively. CONCLUSIONS: Our results suggest that surgery could be avoided in selected patients with rectal cancer who have a cCR to neoadjuvant chemoradiation. However, until the safety of a non-surgical approach is proven in a prospective randomized trial, it cannot be recommended outside a clinical protocol study.

First report of upfront treatment with Gefitinib in comparison with chemotherapy in advanced non-small cell lung cancer patients from south India: Analysis of 120 patients.

BACKGROUND: Lung cancer is the most common cause of cancer deaths in males and sixth among females in south India. Lung cancer is being increasingly recognized among non-smokers. MATERIALS AND METHODS: Stage IIIB and IV advanced non-small cell lung cancer (NSCLC) patients (n=120) treated from January 2009 to December 2010 were retrospectively analyzed. Baseline clinical parameters, treatment protocol, response to therapy and survival were noted. Decision to use upfront Gefitinib was based on parameters like female sex, non-smoking status, adenocarcinoma histology and poor PS. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan Meier method and prognosis by log rank test and Cox regression. RESULTS: BASELINE PARAMETERS: median age: 60 years (22-78 years); male sex: 83 (69.2%); Stage IV: 95(79.2%); adenocarcinoma: 109 (90.8%); smokers: 66 (55%); PS 2/3: 65(54.2%); first-line therapy: Gefitinib: 47 (39.2%), chemotherapy: 73 (60.8%). Among those progressing after chemotherapy, 17 (23%) received second-line Gefitinib. After a median follow-up of 7.5 months (1-26 months), median PFS and OS were 5 months (0-23 months) and 7.5 months (1-26 mo), respectively. On univariate analysis, PFS was significantly improved for non-smokers (7 months vs 4 months, P=0.010), females (7 months vs 5 months, P=0.024) and upfront treatment with Gefitinib (10 months vs 4 months, P=0.014). The only significant factor that affected OS was female sex (18 months vs 9 months, P=0.042). No factors were significant on multivariate analysis. Among PS 2/3 patients, PFS was significantly higher with Gefitinib (n=36) than with single-agent chemotherapy (n=29) [median PFS of 10 months vs 4 months (P=0.017)]. CONCLUSION: In the largest series on the use of first-line Gefitinib from India, we found it to be a useful agent in the treatment of NSCLC, especially in females patients with poor PS and non-smokers, even without Epidermal Growth Factor Receptor (EGFR) mutation testing. Second-line Gefitinib may have negated the OS differences. However, EGFR mutation studies may help in further individualization of therapy.

Etoposide, cisplatin-etoposide, methotrexate, actinomycin-D as primary treatment for management of very-high-risk gestational trophoblastic neoplasia.

OBJECTIVE: To evaluate the efficacy of etoposide, cisplatin-etoposide, methotrexate, actinomycin-D (EP-EMA) chemotherapy as the frontline treatment for gestational trophoblastic neoplasia (GTN) patients with very high (≥ 12) FIGO prognostic scores. METHODS: Nine patients with very-high-risk GTN were treated with EP-EMA at the Cancer Institute, Adyar, India, between January 1, 2001, and December 31, 2007. Salvage chemotherapy, adjuvant surgery, and radiotherapy were used when indicated. Clinical response, toxicity, and survival were analyzed separately. RESULTS: The median FIGO score was 15. Six (66.7%) patients had a complete clinical response, whereas progressive disease occurred for 3 (33.3%) women. None of the patients relapsed. This translated to an overall survival rate of 66.7% in the primary setting. All patients with liver-only metastases were survivors after treatment with EP-EMA. Grade 3 neutropenia was detected in 3 (33.3%) patients only. No life-threatening toxicity was observed after EP-EMA treatment. CONCLUSION: EP-EMA was highly effective for the primary management of very-high-risk GTN.

Cystic renal neoplasm causing hypertension in a 2-year-old child.

Cystic neoplasms of kidney in pediatric age group include a wide variety of tumors, both of benign and malignant pathology. In a child, renal neoplasms with associated hypertension are rare. Here, we present a 2-year-old child who had a multicystic renal tumor with hypertension. She underwent radical nephrectomy subsequent to which hypertension disappeared. The postoperative pathology revealed multicystic nephroma.

Management of high-risk gestational trophoblastic neoplasia with etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine chemotherapy.

OBJECTIVE: To evaluate the efficacy and toxicity of etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMA-CO) chemotherapy for the treatment of high-risk gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Thirty-five patients with high-risk GTN were treated with 196 cycles of EMA-CO between 1997 and 2006. Twenty-nine patients received EMA-CO in the primary setting and another 6 after failure of single-agent chemotherapy. Salvage chemotherapy was offered to selected patients. RESULTS: Of the 29 patients treated with EMA-CO in the primary setting, 22 (75.8%) had a complete clinical response, 5 (17.1%) progressed, and 2 (7.1%) had early deaths. Three patients relapsed after achieving initial complete response. Five were treated with salvage chemotherapy, of which only 2 survived. This translated to overall survival rate of 71% in the primary setting. Five of the 6 patients treated with EMA-CO as second line are survivors. Life threatening toxicity was not seen after EMA-CO. Nine subsequent normal pregnancies were reported after EMA-CO. CONCLUSION: EMA-CO was highly effective for the management of high-risk GTN, and the toxicities were minimal. Reproductive outcome after treatment with EMA-CO was excellent.