Atul Batra

Complete response after autologous stem cell transplant in multiple myeloma.

We evaluated long‐term outcome of patients achieving complete response (CR) after autologous stem cell transplantation (ASCT) for multiple myeloma. Between April 1990 and June 2012 191 patients underwent ASCT. The median age was 53 years (range, 26–68 years), 135 were men. Pretransplant, patients received induction therapy with VAD (vincristine, doxorubicin, dexamethasone; n = 77), novel agents (n = 92), or alkylating agent‐based, n = 22); 43% received more than one line of induction regimen. Response to transplant was defined as per EBMT criteria. The median follow‐up for the entire group was 85 months (range, 6–232.5 months). Following transplant 109 (57.1%) patients achieved CR. Median progression‐free survival (PFS) for patients with CR was higher compared to those with VGPR and PR, (107 vs. 18 vs. 18 months, P < 0.001). Number of lines of therapy pretransplant (one or two vs. more than two lines of therapy (P < 0.001), and absolute lymphocyte count of ≤3000/cmm were predictors of superior PFS. Median overall survival (OS) for patients with CR was higher, (204 months), compared to those with VGPR (71.5 months, P < 0.001) and PR (51.5 months, P < 0.001), respectively. On Cox regression analysis, patients who received one line of induction therapy pretransplant (hazard ratio, HR 2.154, P < 0.001) and those with absolute lymphocyte count of ≤3000/mm3 (HR 0.132, P < 0.001) had superior PFS. For overall survival, induction treatment up to one line (HR 2.403, P < 0.004) and Hb > 7.1 G/dL at diagnosis (HR 4.756, P < 0.01) were associated with superior outcome. On landmark analysis at 12 months, PFS and OS continued to remain superior for patients attaining CR. Achievement of CR post transplant is associated with longer OS and PFS. Among complete responders, those who receive one line of induction therapy pretransplant have superior outcome.

Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors: A Randomized Clinical Trial

Importance Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence. Objectives To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy. Design, Setting, and Participants A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options. Interventions One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression. Main Outcomes and Measures The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points. Results A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than 3 cycles (HR for PFS, 0.46; 95% CI, 0.23-0.93; P = .03) and those without a bone sarcoma (ie, neither primitive neuroectodermal tumor nor osteosarcoma) (HR for PFS, 0.39; 95% CI, 0.18-0.81; P = .01) appeared to benefit from metronomic chemotherapy. Conclusions and Relevance Metronomic chemotherapy does not improve 6-month PFS, compared with placebo, among pediatric patients with extracranial progressive solid malignant tumors . However, patients without bone sarcoma and those able to tolerate therapy for more than 3 cycles (9 weeks) benefit. Trial Registration clinicaltrials.gov Identifier: NCT01858571.

Developing a prognostic model for patients with localized osteosarcoma treated with uniform chemotherapy protocol without high dose methotrexate: A single‐center experience of 237 patients

Studies of baseline prognostic factors in patients with localized osteosarcoma treated without high dose methotrexate are limited.

Quality of Life Assessment in Retinoblastoma: A Cross-Sectional Study of 122 Survivors from India.

With current modalities, cure rates of retinoblastoma are high and hence the number of survivors is increasing. However, data on quality of life (QOL) are minimal.

Ototoxicity in retinoblastoma survivors treated with carboplatin based chemotherapy: A cross-sectional study of 116 patients

To the Editor: Unlike cisplatin, ototoxicity with carboplatin in patients with retinoblastoma has been reported to range from 0% to 79%.[1–4] This is a cross-sectional study to evaluate hearing loss in retinoblastoma survivors, who had completed therapy for more than 12 months and were more than 5 years of age at assessment. We evaluated 116 retinoblastoma survivors with median age of 99 (range, 60–248) months at assessment. Median age at diagnosis was 36 (range, 0–192) months with a male/female ratio of 2.4. Onefourth of survivors had bilateral disease at presentation. Extraocular disease was seen in 14% (16/116) of patients, of which two patients (2%) had metastatic disease. Eighty-five percent patients received vincristine, etoposide, and carboplatin (VEC) based chemotherapy regimen. The dose of carboplatin given in each cycle was 560mg/ m (18.6mg/kg in children less than 3 years). Radiotherapy was given in 22% of the patients.Median number of cycles was 6 (range, 2–15) with mean cumulative carboplatin dose of 4,132 2,476 (median: 3,360) mg/m. Median follow-up duration from treatment completion was 66 (range, 18–130) months. Hearing loss was assessed using pure tone audiometry at a frequency range of 750–8,000Hz and graded as per Brock’s scale.[5] One patient was found to have Brock’s grade I bilateral sensory-neural hearing loss ( 40 dB at 8,000Hz). This patient was a 7-year-old male who was diagnosed as group E retinoblastoma at 3 years of age and received six cycles of VEC as chemoprevention after enucleation; the cumulative dose of carboplatin was 3,360mg/m. Retrospective review of records did not reveal exposure to radiotherapy or use of aminoglycosides, loop diuretics, or cisplatin in this patient. Hearing loss of even 20 dB was not observed in any other patient. We found that hearing loss was infrequent in retinoblastoma survivors. This was similar to that observed in healthy school going children in Southern India.[6] Carboplatin-induced hearing loss in pediatric population has been reported inconsistently from 0% to 79% with cumulative dose ranging from 1,020 to 8,400mg/m. [3,4,7,8] Variable definitions of hearing loss andmethods of hearing assessment, cumulative dose of carboplatin, concurrent use of aminoglycosides, loop diuretics, and other ototoxic drugs, and heterogenous populations with varying sensitivity to carboplatin may be few reasons for this inconsistency. In our patients, the median age at diagnosis was 36months versus 18months in western population; age less than 6 months at carboplatin exposure has been associated with sensory-neural hearing loss.[4,9] This could be one of the reasons for infrequent hearing loss observed in this study. Strengths of the study include a large study population and long duration of follow-up after treatment completion, as ototoxicity of carboplatin is known to increase with time.[10] The study was limited by cross-sectional design and absence of baseline and periodic hearing evaluation. Although the hearing loss observed in this study was less than 1%, a recommendation against routine hearing evaluation cannot be made in the absence of long-term prospective studies.

Diagnostic Dilemma in Cornual Pregnancy- 3D Ultrasonography may Aid!!

Interstitial or cornual pregnancy is a rare and dangerous type of ectopic gestation. It poses a diagnostic difficulty and differentiating from eccentrically located intrauterine pregnancy may be challenging. We are reporting a case of nulliparous woman diagnosed as having interstitial pregnancy on three-dimensional ultrasonography. We managed the patient successfully with weekly intramuscular doses of methotrexate. The β HCG levels were high throughout the therapy (89,000 to 1,48,000 IU/ml). The patient was admitted throughout the course of treatment. After three doses of methotrexate, the β-HCG levels began to fall. Weekly monitoring was done thereafter till normal values of β-HCG were reported. Early and prompt diagnosis and treatment of interstitial pregnancy is important to prevent catastrophic hemorrhagic complications. Three-dimensional sonography is an important diagnostic tool as it may impart better anatomical orientation and precise location of the gestational sac as compared to other imaging modalities. Methotrexate therapy may be considered in selected cases.

Parents’ Perspective of Quality of Life of Retinoblastoma Survivors

Health‐related quality of life (HRQOL) in retinoblastoma survivors was assessed using parent proxy report of PedsQLTM 4.0 generic core scale. One hundred twenty‐two parents of retinoblastoma survivors filled the questionnaire satisfactorily. This was compared with parent‐reported HRQOL of 50 siblings. The median age of survivors was 98 (range, 60–247) months and male:female ratio was 2:1. The overall parent‐reported HRQOL was significantly worse in survivors as compared to controls (74.4 ± 8.5 vs. 85.1 ± 4.6, P < 0.001). All health domains were significantly affected when compared with controls. None of the baseline and treatment‐related factors predicted HRQOL.

Aprepitant for paediatric chemotherapy-induced nausea and vomiting

e259 www.thelancet.com/oncology Vol 16 June 2015 comor bidities (specifi cally cardiovascular risk factors) of patients in both treatment groups and did not fi nd signifi cant diff erences (data not shown). We believe that the signifi cant diff erence in overall survival shown in our Kaplan-Meier plots is consistent with the corresponding diff erence in biochemical disease-free survival and, more importantly, with the diff erence in metastasis-free survival. Our results showed that, com pared with short-term androgen deprivation, 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical disease-free survival, metastasisfree survival, and overall survival in patients with high-risk prostate cancer. These fi ndings are consistent with those reported elsewhere.

Skin metastasis: a rare presentation in testicular germ cell tumour

A 35-year-old man presented with a history of cough, haemoptysis, weight loss for 2 months along with ulceroproliferative lesions on the chin and the scalp. On evaluation he was found to have non-seminomatous germ cell tumour, stage 3 c, poor risk with Eastern Cooperative Oncology Group Performance Status of 4. The skin lesions were proven to be metastasis by fine-needle aspiration cytology. He showed significant improvement with a 3-day protocol of abbreviated etoposide and cisplatin chemotherapy and is planned for 4 cycles of VIP. This case describes an uncommon presentation of germ cell tumour in the form of skin metastasis with excellent response to chemotherapy.

Association of energy intake and expenditure with obesity: A cross-sectional study of 150 pediatric patients following treatment for leukemia

ABSTRACT Increased obesity in leukemia survivors has been attributed to chemotherapy and radiation. Data on total energy intake (TEI) and total energy expenditure (TEE) are lacking in obese childhood leukemia patients after completion of therapy from India. We conducted a cross-sectional study in pediatric acute leukemia patients after completion of therapy wherein energy intake was assessed by 24-hour recall method. TEE was calculated using Harris–Benedict equation, by assessing the physical activity level using Physical Activity Questionnaire for children and basal metabolic rate by World Health Organization equation. Indian Academy of Pediatrics 2015 guidelines for BMI were used for defining overweight and obesity. Nutritional status was assessed in 150 leukemia patients after completion of therapy. Twenty-five percent of leukemia patients after completion of therapy were overweight and obese versus 11% of healthy controls (p = 0.042). The mean ratio of TEI/required energy intake (REI), TEE/required energy expenditure (REE), and (TEI:REI)/(TEE:REE) were significantly higher in overweight and obese group versus nonobese survivors (p < 0.001, p = 0.091, p < 0.001, respectively). Multivariate analysis showed higher income (HR-2.3, p = 0.04), increased TEI/REI (HR-4, p = 0.049) and higher (TEI:REI)/(TEE:REE) (HR-3.1, p = 0.039) to be significant factors predicting obesity. Obesity in leukemia patients after completion of therapy is associated with increased energy intake, causing imbalance between energy intake and TEE in these patients.