Manjula Maganti

Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

PURPOSEnReported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation.nnnMETHODS AND MATERIALSnA prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses at the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest.nnnRESULTSnCases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse.nnnCONCLUSIONSnIncidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.

The sooner the better: Genetic testing following ovarian cancer diagnosis

OBJECTIVEnAs treatment based genetic testing becomes a reality, it is important to assess the attitudes and preferences of women newly diagnosed with ovarian cancer regarding genetic testing. The objective of this study was to determine when women with a diagnosis of high grade serous ovarian cancer would prefer to undergo genetic testing and factors that influence this preference.nnnMETHODSnWomen over 18years of age with a known diagnosis of high grade serous ovarian cancer diagnosed between October 2010-2013 were identified via the Princess Margaret Cancer Center Registry. Participants completed a questionnaire, which obtained preferences and attitudes towards genetic testing, cancer history, and demographic information.nnnRESULTSn120 of the 355 women identified (33.8%) completed the questionnaires. The median age at time of ovarian cancer diagnosis was 57years (range 35-84). The majority of participants in this study were offered (94.6%) and pursued (84.8%) genetic testing. In this cohort, testing was most frequently offered at diagnosis (41.8%) or during treatment (19.1%). In this study, women with high grade serous ovarian cancer felt that genetic testing should be offered before or at the time of diagnosis (67.8%). Having a family history of breast or ovarian cancer was significantly (p=0.012) associated with preferring genetic testing at an earlier time point in the disease course.nnnCONCLUSIONSnOur results demonstrate that women with high grade serous ovarian cancer acknowledge the personal and clinical utility of genetic testing and support test implementation at the time of cancer diagnosis.

Clinical Features of Patients With Philadelphia-Negative Myeloproliferative Neoplasms Complicated by Portal Hypertension

BACKGROUNDnPortal hypertension has been reported to afflict 7% to 18% of patients with Philadelphia-negative MPNs, with complications of variceal bleeding and ascites. The clinical features and outcomes of these patients are unclear.nnnPATIENTS AND METHODSnIn this multicenter retrospective study, we evaluated the clinical features of 51 patients with MPNs complicated by PHTN.nnnRESULTSnThe diagnosis of underlying MPN was most frequently PV (39%) and primary MF (35%), followed by post-PV MF (18%), ET (4%), and post-ET MF (4%). Frequency of Janus Kinase 2 V617F mutation appears as expected in the underlying MPN. Thrombosis within the splanchnic circulation was prevalent in patients with polycythemia compared with other MPNs (76% vs. 26%; P = .0007).nnnCONCLUSIONnPV and MF patients have a greater incidence of PHTN in our population, with thrombosis contributing to PHTN development in PV patients. Patients with splanchnic circulation thrombosis are potential candidates for screening for PHTN. These data might be useful for developing screening strategies for early detection of PHTN in patients with MPN.

Clinical characteristics and early treatment outcomes of follicular lymphoma in young adults

Follicular lymphoma (FL) in young adults (YA, <40 years old) is uncommon, and the clinical characteristics and outcomes of this group are not well defined. We conducted a retrospective database review of 427 patients with newly diagnosed FL aged 65 years or less registered at Princess Margaret Cancer Centre between 1995 and 2010. YA (n = 61) and those 40–65 (n = 366) were compared with regards to clinical stage at diagnosis, FL International Prognostic Index (FLIPI) score, and the following clinical outcomes: time to second treatment, cause‐specific survival (CSS) and overall survival (OS). At diagnosis, stage and FLIPI score were similar, as were the proportion of patients requiring therapy (YA 75% versus older adults 71%). Median follow‐up was 8·1 years. Time to second therapy was similar in both age groups (5‐year probability 23% YA versus 27% older adults; Grays P‐value = 0·76). Ten‐year OS was significantly higher for YA (87% versus older adults 72%; P = 0·029). On multivariate analysis, age <40 years, low FLIPI score and observation as initial management were favourable prognostic factors for OS and CSS. We conclude that YA with FL have a favourable prognosis compared to older patients; whether this reflects competing mortality risks or age‐related differences in lymphoma biology warrants further investigation.

All in the Family: Barriers and Motivators to the Use of Cancer Family History Questionnaires and the Impact on Attendance Rates

Data has demonstrated that family history questionnaires (FHQs) are an invaluable tool for assessing familial cancer risk and triaging patients for genetic counseling services. Despite their benefits, return rates of mailed FHQs from newly referred patients remain low, suggesting potential barriers to their use. To investigate this, a total of 461 participants, 239 who completed a FHQ (responders) and 222 who did not (non-responders), were surveyed at a subsequent appointment regarding potential barriers and motivators to using the FHQ. With respective rates of 51 and 56xa0%, there was no significant difference in the proportion of responders and non-responders who reported difficulty in completing the FHQ; however, for both groups factors related to family dynamics (large family size, lack of contact with relatives, and lack of knowledge of family history) were reported as major variables confounding completion of the FHQ. Responders were also significantly more likely to have a personal diagnosis of cancer (pu2009=u20090.02) and to report that their physician had discussed the reason for the appointment with them (pu2009=u20090.01). Overall, 19xa0% of non-responders returned their FHQ after being mailed an appointment letter and 67xa0% attended their scheduled genetic counseling appointment. These findings demonstrate that difficulty completing the FHQ is not inherent to its design but due to difficulty accessing one’s family history, and that mailed appointment letters are a highly successful way to increase attendance rates in the non-responder population. Furthermore, these results demonstrate the important role that referring physicians play in the utilization of genetic counseling services.

Prevention of carboplatin-induced hypersensitivity reactions in women with ovarian cancer:

Background Carboplatin-based chemotherapy offers high response rates and improved overall survival for women with epithelial ovarian cancer, but its use is limited by the occurrence of hypersensitivity reactions. To evaluate the efficacy of prophylactic diphenhydramine for hypersensitivity reaction prevention, we reviewed the incidence of hypersensitivity reactions and identified patients at high risk of hypersensitivity reactions. Methods Women receiving ≥6 cycles of carboplatin-based chemotherapy for epithelial ovarian cancer were identified from our institutional database at the Princess Margaret Cancer Centre. Institutional policy was changed in 2009 to introduce diphenhydramine prophylaxis for patients receiving ≥6 cycles of carboplatin. Additional clinical data were abstracted from the patient record. Results Between 2006 and 2012, 450 women received ≥6 cycles of carboplatin-based chemotherapy for epithelial ovarian cancer. Two hundred and ninety-one women received prophylaxis with diphenhydramine. Carboplatin-induced hypersensitivity reactions occurred in 41 of 449 patients (9%). Univariable predictors of carboplatin-induced hypersensitivity reactions included administration of 8 to 10 cycles of carboplatin, history of other drug allergies and a platinum-free interval >12 months. BRCA mutational status was not predictive. In a multivariable analysis, the number of cycles of carboplatin and a platinum-free interval >12 months were independent predictors of hypersensitivity reactions. There was a trend towards diphenhydramine prophylaxis reducing the incidence of hypersensitivity reactions in women with a platinum-free interval compared to continuous delivery; this was most marked when the platinum-free interval was >12 months (nu2009=u200964) (OR: 0.2 (95% CI: 0.046–0.83), pu2009=u20090.03). Conclusions The administration of diphenhydramine to women who have a platinum-free interval may reduce the risk of hypersensitivity reaction, but prospective evaluation is required.

Comparison of two novel staging systems with the TNM system in predicting stage III colon cancer survival

Adaptations of the TNM staging system that incorporate the Lymph Node Ratio (LNR) have been proposed for stage III colon cancer. This study compared the concordance of two novel staging systems and the TNM system with observed survival outcomes in stage III patients.

Single-center Experience in Treating Patients With t(4;14) Multiple Myeloma With and Without Planned Frontline Autologous Stem Cell Transplantation

&NA; This retrospective study analyzed the long‐term outcome of 75 patients with t(4;14) multiple myeloma treated in a single center with frontline bortezomib‐based treatment. Frontline autologous stem cell transplant following bortezomib‐based induction was associated with better progression‐free survival. These results further support the use of frontline autologous stem cell transplant, especially among patients with high‐risk cytogenetics. Background: Translocation t(4;14) has traditionally been classified as a high‐risk cytogenetic feature in patients with multiple myeloma with shortened progression‐free (PFS) and overall survival (OS) despite initial response to treatment. Recent data have shown an improved long‐term survival in these patients treated with novel agents, such as bortezomib. Patients and Methods: We conducted a retrospective study on our patients with t(4;14) multiple myeloma treated with bortezomib‐based induction between July 1, 2006 and June 30, 2014 to assess the real‐world outcomes of these patients in a tertiary center. Results: Among the 75 patients analyzed, the median PFS was 33.5 months, and the median OS was 69.6 months after a median follow‐up of 41 months. Even in the era of novel agents, patients who received frontline autologous stem cell transplant had a better PFS than those who received chemotherapy alone (median PFS, 24.2 months vs. 41.5 months; P = .01). Hypercalcemia at the time of presentation was found to be a significant predictor of progression (hazard ratio [HR], 10.1; 95% confidence interval [CI], 4.0‐26.0) and death (HR, 9.4; 95% CI, 3.2‐27.8), and co‐harboring of del(17p) by fluorescent in situ hybridization with t(4;14) was associated with a significantly inferior OS (HR, 4.0; 95% CI, 1.4‐11.4). Conclusion: Even in the era of novel agents, t(4;14) remains a negative prognostic marker. Frontline autologous stem cell transplant remains as an essential tool when treating these high‐risk patients, but further prospective randomized studies are needed to determine the most effective strategy for this patient group.

Correlation of Neutrophil to Lymphocyte Ratio and Absolute Neutrophil Count With Outcomes With PD-1 Axis Inhibitors in Patients With Advanced Non–Small-Cell Lung Cancer

Micro‐Abstract: Programmed death‐1 (PD‐1) axis inhibitors have become standard therapy in advanced Non–Small‐Cell Lung Cancer (NSCLC). The relationship between clinical outcomes and neutrophil to lymphocyte ratio (NLR) and absolute neutrophil count (ANC) was explored in 88 advanced NSCLC patients treated with PD‐1 axis inhibitors. Patients with baseline NLR ≤4 had superior disease control rate, treatment duration, and survival. Lower NLR and ANC during treatment were associated with response and treatment duration. Introduction: Programmed death‐1 (PD‐1) axis inhibitors have become standard therapy in advanced non–small‐cell lung cancer (NSCLC). Response might be delayed and pseudo‐progression occasionally occurs in patients who eventually benefit from treatment. Additional markers beyond programmed death ligand 1 (PD‐L1) expression are needed to assist in patient selection, response evaluation, and treatment decisions. Materials and Methods: The relationship between prospectively collected clinical outcomes (response, disease control rate [DCR], treatment duration, overall survival) and hematologic parameters (neutrophil to lymphocyte ratio [NLR], absolute neutrophil count [ANC], and platelet to lymphocyte ratio [PLR]) was explored retrospectively in advanced NSCLC patients treated with PD‐1 axis inhibitors at a major cancer center from May 2013 to August 2016. Hematologic parameters at baseline and during treatment (week 2 or 3 and week 8) were included. Results: Of 88 patients treated with PD‐1 axis inhibitors, 22 (25%) experienced partial response. Baseline NLR ≤4 was associated with superior DCR (74% vs. 50%; P = .025), treatment duration (P = .037), time to progression (P = .053), and overall survival (P = .019), with no differential association according to PD‐L1 tumor expression. Lower NLR and ANC during treatment were also associated with response to treatment (P = .025 and P = .017, respectively), and treatment duration (P = .036 and P = .008). No association was found between baseline PLR and DCR, response, treatment duration, nor overall survival. Conclusion: Baseline NLR ≤4 and lower NLR and ANC during treatment might correlate with disease control and treatment response and should be explored further as potential predictors of treatment benefit in larger studies.

18 F-FDG PET/CT metabolic tumor parameters and radiomics features in aggressive non-Hodgkin’s lymphoma as predictors of treatment outcome and survival

PurposeTo determine whether metabolic tumor parameters and radiomic features extracted from 18F-FDG PET/CT (PET) can predict response to therapy and outcome in patients with aggressive B-cell lymphoma.MethodsThis institutional ethics board-approved retrospective study included 82 patients undergoing PET for aggressive B-cell lymphoma staging. Whole-body metabolic tumor volume (MTV) using various thresholds and tumor radiomic features were assessed on representative tumor sites. The extracted features were correlated with treatment response, disease-free survival (DFS) and overall survival (OS).ResultsAt the end of therapy, 66 patients (80.5%) had shown complete response to therapy. The parameters correlating with response to therapy were bulky diseaseu2009>u20096xa0cm at baseline (pu2009=u20090.026), absence of a residual massu2009>u20091.5xa0cm at the end of therapy CT (pu2009=u20090.028) and whole-body MTV with best performance using an SUV threshold of 3 and 6 (pu2009=u20090.015 and 0.009, respectively). None of the tumor texture features were predictive of first-line therapy response, while a few of them including GLNU correlated with disease-free survival (pu2009=u20090.013) and kurtosis correlated with overall survival (pu2009=u20090.035).ConclusionsWhole-body MTV correlates with response to therapy in patient with aggressive B-cell lymphoma. Tumor texture features could not predict therapy response, although several features correlated with the presence of a residual mass at the end of therapy CT and others correlated with disease-free and overall survival. These parameters should be prospectively validated in a larger cohort to confirm clinical prognostication.