S. Hamilton

Treatment and Outcomes in Patients With Primary Cutaneous B-Cell Lymphoma: The BC Cancer Agency Experience

PURPOSE To review the treatment and outcomes of patients with primary cutaneous B-cell lymphoma (CBCL). METHODS AND MATERIALS Clinical characteristics, treatment, and outcomes were analyzed for all patients referred to our institution from 1981 through 2011 with primary CBCL without extracutaneous or distant nodal spread at diagnosis (n=136). Hematopathologists classified 99% of cases using the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) guidelines. RESULTS Median age at diagnosis was 62 years. Classification was 18% diffuse large B-cell leg-type (DLBCL-leg), 32% follicle center (FCCL), 45% marginal zone (MZL), and 6% nonclassifiable (OTHER). Of the 111 subjects with indolent lymphoma (FCCL, MZL, OTHER), 79% received radiation alone (RT), 11% surgery alone, 3% chemotherapy alone, 4% chemotherapy followed by RT, and 3% observation. Following treatment, 29% of subjects relapsed. In-field recurrence occurred in 2% treated with RT and in 33% treated with surgery alone. Of the 25 subjects with DLBCL-leg, 52% received chemotherapy followed by RT, 24% chemotherapy, 20% RT, and 4% surgery alone. Seventy-nine percent received CHOP-type chemotherapy (cyclophosphamide, doxorubicin or epirubicin, vincristine, prednisone), 47% with rituximab added. Overall and disease-specific survival and time to progression at 5 years were 81%, 92%, and 69% for indolent and 26%, 61%, and 54% for DLBCL-leg, respectively. On Cox regression analysis of indolent subjects, RT was associated with better time to progression (P=.05). RT dose, chemo, age>60 y, and >1 lesion were not significantly associated with time to progression. For DLBCL-leg, disease-specific survival at 5 years was 100% for those receiving rituximab versus 67% for no rituximab (P=.13). CONCLUSIONS This review demonstrates better outcomes for indolent histology compared with DLBCL-leg, validating the prognostic utility of the WHO-EORTC classification. In the indolent group, RT was associated with 98% local control. DLBCL-leg is a more aggressive disease; the excellent results in the rituximab group suggest it has an important role in management.

Incidence of second malignancies in prostate cancer patients treated with low-dose-rate brachytherapy and radical prostatectomy.

PURPOSE To compare the second malignancy incidence in prostate cancer patients treated with brachytherapy (BT) relative to radical prostatectomy (RP) and to compare both groups with the cancer incidence in the general population. METHODS AND MATERIALS From 1998 to 2010, 2418 patients were treated with Iodine 125 prostate BT monotherapy at the British Columbia Cancer Agency, and 4015 referred patients were treated with RP. Cancer incidence was compared with the age-matched general population using standardized incidence ratios (SIRs). Pelvic malignancies included invasive and noninvasive bladder cancer and rectal cancer. Cox multivariable analysis was performed with adjustment for covariates to determine whether treatment (RP vs BT) was associated with second malignancy risk. RESULTS The median age at BT was 66 years and at RP 62 years. The SIR comparing BT patients with the general population was 1.06 (95% confidence interval [CI] 0.91-1.22) for second malignancy and was 1.53 (95% CI 1.12-2.04) for pelvic malignancy. The SIR comparing RP patients with the general population was 1.11 (95% CI 0.98-1.25) for second malignancy and was 1.11 (95% CI 0.82-1.48) for pelvic malignancy. On multivariable analysis, older age (hazard ratio [HR] 1.05) and smoking (HR 1.65) were associated with increased second malignancy risk (P<.0001). Radical prostatectomy was not associated with a decreased second malignancy risk relative to BT (HR 0.90, P=.43), even when excluding patients who received postprostatectomy external beam radiation therapy (HR 1.13, P=.25). Older age (HR 1.09, P<.0001) and smoking (HR 2.17, P=.0009) were associated with increased pelvic malignancy risk. Radical prostatectomy was not associated with a decreased pelvic malignancy risk compared with BT (HR 0.57, P=.082), even when excluding postprostatectomy external beam radiation therapy patients (HR 0.87, P=.56). CONCLUSIONS After adjustment for covariates, BT patients did not have an increased second malignancy risk compared with RP patients. Further follow-up of this cohort is needed given the potential latency of radiation-induced malignancies.

Population-based outcomes after brain radiotherapy in patients with brain metastases from breast cancer in the Pre-Trastuzumab and Trastuzumab eras

PurposeTo evaluate the survival of patients with human epidermal growth factor receptor 2 (HER2) positive and negative metastatic breast cancer irradiated for brain metastases before and after the availability of trastuzumab (T).Materials and methodsWomen diagnosed with brain metastasis from breast cancer in two eras between 2000 and 2007 (T-era, n = 441) and 1986 to 1992 (PreT-era, n = 307), treated with whole brain radiotherapy (RT) were identified. In the T-era, HER2 testing was part of routine clinical practice, and in the preT-era 128/307 (42%) cases had HER2 testing performed retrospectively on tissue microarrays. Overall survival (OS) was estimated using the Kaplan-Meier method and comparisons between eras used log-rank tests.ResultsIn the preT- and T-era cohorts, the rate of HER2 positivity was 40% (176/441) and 26% (33/128) (p < 0.001). The median time from diagnosis to brain RT was longer in the preT-era (3.3 years versus 2.3 years, p < 0.001). Survival after brain RT was improved in the T-era compared to the preT-era (1-year OS 26% versus 12%, p < 0.001). The 1-year OS rate for HER2 negative patients was 20% in both eras (p = 0.97). Among HER2 positive patients, the 1-year OS in the preT-era was 5% compared to 40% in the T-era (p < 0.001).ConclusionsDistinct from patients with HER2 negative disease in whom no difference in survival after brain RT was observed over time, patients with HER2 positive brain metastases experienced significantly improved survival subsequent to the availability of trastuzumab.

Long-term Outcomes and Complications in Pediatric Ewing Sarcoma.

Objectives: The objective of this study was to determine treatment outcomes and long-term complications in pediatric patients with Ewing Sarcoma treated at the British Columbia Cancer Agency (BCCA). Methods: A retrospective chart review of 101 pediatric patients (<19 y old) with Ewing Sarcoma diagnosed between 1960 and 2005 was performed. The Kaplan-Meier survival analysis and Cox regression multivariate analysis were used to assess prognostic factors for overall survival (OS) and event-free survival (EFS). Results: The median age at diagnosis was 11 years and the median follow-up for nondeceased patients was 13.5 years. The most common primary tumor locations were lower extremity (33%), pelvis (24%), and thorax (18%). Fifty percent of patients received surgery, 79% radiotherapy and 94% chemotherapy. The 5-year OS and EFS for patients with localized disease was 85% and 73% and for metastatic disease was 27% (P<0.0001) and 28% (P<0.0001), respectively. Metastatic disease was an independent predictor of lower OS (hazard ratio [HR], 9.5; 95% confidence interval [CI],4.7-19.4; P<0.0001) and EFS (HR, 4.9; 95% CI, 2.7-8.8; P<0.0001). Extremity tumor location was an independent predictor for improved OS (HR, 0.4; 95% CI, 0.2-0.9; P=0.03). The majority (77%) of long-term survivors (≥5 y) had long-term complications; the most common were musculoskeletal abnormalities (50%) and cardiac toxicity (28%). The actuarial second neoplasm risk was 5% at 10 years. Conclusions: Ewing sarcoma patients with localized disease had excellent treatment outcomes at the BCCA. However, the majority of patients had chronic complications from treatment. This study validates the need for long-term follow-up of Ewing Sarcoma survivors for management of late effects.

Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American Population-based Analysis.

Objectives:The effect of ethnicity on nasopharyngeal cancer (NPC) outcomes is unclear. This retrospective analysis examines survival and the impact of concurrent chemoradiation (chemoRT) among Asian and non-Asian patients. Methods:Subjects included 380 consecutive patients with NPC treated at a Canadian institution from 2000 to 2009. Five-year Kaplan-Meier progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were compared between Asian (n=279) and non-Asian (n=101) subjects. Multivariable analysis was performed using Cox regression modeling. Two-variable interaction terms with concurrent chemoRT were used to examine whether concurrent chemoRT conferred different effects among subgroups. Results:Asian subjects presented with earlier stage (P=0.005), were younger, had better performance status, and were less likely smokers (all P<0.001). Survival among Asian versus non-Asian subjects with stage I/II NPC were: PFS 68% versus 59% (P=0.04), DSS 87% versus 77% (P=0.08), and OS 84% versus 74% (P=0.003). Corresponding rates with stage III/IVA/IVB disease were PFS 49% versus 42% (P=0.12), DSS 72% versus 46% (P=0.001), and OS 70% versus 44% (P<0.001). On multivariable analysis, Asian ethnicity, age below 65 years, ECOG performance status 0-1, early stage, staging MRI use, and concurrent chemoRT were associated with improved DSS and OS (P<0.05). On testing interactions with concurrent chemoRT, Asian versus non-Asian ethnicity was significant (hazard ratio 3.9), suggesting that concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects. Conclusions:In this population-based study, Asian ethnicity was associated with improved DSS and OS. Concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects.

Impact of Neoadjuvant Chemotherapy on the Administration of Concurrent Chemoradiation for Locally Advanced Nasopharyngeal Carcinoma

Objectives The standard of care for locally advanced nasopharyngeal carcinoma (NPC) is concurrent cisplatin chemoradiotherapy. Neoadjuvant chemotherapy can be administered to downsize tumors before concurrent treatment to optimize radiation volumes. Our hypothesis was that the use of cisplatin in the neoadjuvant phase could limit the amount of cisplatin that patients could tolerate in the concurrent phase of treatment. Methods This is a retrospective analysis of Canadian NPC patients who received neoadjuvant chemotherapy with the intention to downsize locally advanced tumors prior to concurrent cisplatin plus radiation. Baseline demographic and treatment data were obtained from institutional databases and chart review; all data were analyzed with SPSS (SPSS Inc. Released 2005. SPSS for Windows, Version 14.0. Chicago: SPSS Inc.) Overall survival (OS), disease-specific survival (DSS), and local/regional relapse-free survival (LRRFS) were analyzed using Kaplan-Meier survival functions. Univariate and multivariate models were used to determine factors associated with the total dose of concurrent chemotherapy. Results Forty-six patients were identified as receiving neoadjuvant chemotherapy before concurrent chemoradiotherapy. In the univariate and multivariate analyses of patients who received concurrent chemotherapy, receiving over 200 mg/m2 concurrent cisplatin with radiation was associated with a higher neoadjuvant dose of chemotherapy received. The median follow-up time was 2.6 years (range, 0.17 years to 10.6 years). At three years, the OS was 83%, DSS was 86%, and LRRFS was 74%. Conclusions NPC patients have been treated with neoadjuvant chemotherapy at this center with favorable outcomes. Most patients could tolerate concurrent chemotherapy after radiotherapy. Receiving higher doses of concurrent chemotherapy was associated with also having higher doses of neoadjuvant cisplatin. This suggests that neoadjuvant cisplatin is not a limiting factor in the delivery of full-dose concurrent chemotherapy.

Magnetic Resonance Imaging Volumetry of Primary Nasopharyngeal Cancer in Patients Treated with Induction Gemcitabine and Cisplatin Followed by Concurrent Cisplatin and Volumetric Modulated Arc Therapy

Introduction The addition of induction chemotherapy (IC) to the standard concurrent chemoradiotherapy (CCRT) is under consideration in locally advanced nasopharyngeal carcinoma (LANPC). To-date, no studies have reported primary gross tumour volume (GTVp) changes using gemcitabine and cisplatin as the IC phase in LANPC. We investigated the timing and magnitude of GTVp response throughout sequential gemcitabine and cisplatin IC and CCRT for LANPC. Toxicity and tumour control probability (TCP) analyses are also presented Methods Ten patients with LANPC underwent sequential IC and CCRT between 2011 and 2015. All patients had magnetic resonance imaging (MRI) at three time points: before IC (MRI0), after IC (MRI1), and three months after CCRT (MRI3). Five of the 10 patients had an additional MRI four to five weeks into CCRT (MRI2). GTVp contours were delineated retrospectively using contrast-enhanced MRIs, and each GTVp underwent secondary review by a neuroradiologist. Acute toxicities were graded retrospectively via chart review based on the National Cancer Institute Common Terminology for Adverse Events version 4.0 (NCI CTCAE v4.0). Results Mean GTVp reduction between MRI0 - MRI1 was from 68 cc to 47 cc and from 47 cc to 9 cc between MRI1 - MRI3. In patients with MRI2, the mean GTVp reduction between MRI1 - MRI2 was from 57 cc to 32 cc. Tumour control probability estimates increased by 0.11 after IC. Patients tolerated the treatment well with one Grade IV toxicity event. Conclusion The observed GTVp response and improved tumor control probability support further investigation into the use of IC in LANPC.