Jeffrey M. Switchenko

Rising Incidence of Mucosal Melanoma of the Head and Neck in the United States

Background. While it is established that the incidence of cutaneous melanoma has risen over time in the United States, the incidence trend for mucosal melanoma of the head and neck (MMHN) is unknown. Methods. We used the Surveillance, Epidemiology, and End Results (SEER) database to determine incidence trends for MMHN from 1987 to 2009 in the United States. We determined annual percent change (APC) by weighted least squares and joinpoint regression analysis. Results. MMHN incidence increased from 1987 to 2009 (APC 2.4%; P < 0.01). Nasal cavity lesions increased in incidence (APC 2.7%; P < 0.01) over this duration, while the incidence of non-nasal cavity lesions remained stable. The highest rate of increase was in white females ages 55 to 84 (APC 5.1%; P = 0.01). Conclusions. The incidence of MMHN in the United States has been rising since 1987. This trend is driven primarily by increased incidence of nasal cavity melanomas.

Chemoradiation therapy sequencing for resected pancreatic adenocarcinoma in the National Cancer Data Base.

Pancreatic adenocarcinoma (PAC) has low overall survival (OS) rates and high recurrence rates following surgical resection. The role for preoperative radiation therapy (prRT) for PAC versus postoperative RT (poRT) remains uncertain. The authors used the National Cancer Data Base (NCDB) to report prRT outcomes for the largest multi‐institutional patient cohort to date.

BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis.

We retrospectively compared the outcomes and toxicities of melanoma brain metastases (MBM) patients treated with BRAF inhibitors (BRAFi) and stereotactic radiosurgery (SRS) with SRS alone. We identified 87 patients with 157 MBM treated with SRS alone from 2005 to 2013. Of these, 15 (17.2%) patients with 32 MBM (21.4%) received BRAFi therapy: three (20.0%) before SRS, two (13.3%) concurrent, and 10 (66.7%) after SRS. Overall survival (OS) was compared between cohorts using the product limit method. Intracranial outcomes were compared using cumulative incidence with competing risk for death. Baseline patient characteristics were similar between groups, except for the SRS cohort, which had higher rates of chemotherapy and more recent year of diagnosis. Radiation characteristics, including dose per fraction, total dose, gross tumor volume size, and prescription isodose, were also similar between cohorts. One-year outcomes – OS (64.3 vs. 40.4%, P=0.205), local failure (3.3 vs. 9.6%, P=0.423), and distant intracranial failure (63.9 vs. 65.1%, P=0.450) were not statistically different between the SRS+BRAFi and SRS-alone groups, respectively. The SRS+BRAFi group showed higher rates of radiographic radiation necrosis (RN) (22.2 vs. 11.0% at 1 year, P<0.001) and symptomatic radiation necrosis (SRN) (28.2 vs. 11.1% at 1 year, P<0.001). Multivariable analysis showed that BRAFi predicted an increased risk of both radiographic and SRN. SRS and BRAFi predicted for an increased risk of radiographic and SRN compared with SRS alone. Approaches to mitigate RN for patients receiving SRS and BRAFi should be considered until the clinical trial (http//:www.clinicaltrials.gov: NCT01721603) evaluating this treatment regimen is completed.

Single-Isocenter Multiple-Target Stereotactic Radiosurgery: Risk of Compromised Coverage

PURPOSE To determine the dosimetric effects of rotational errors on target coverage using volumetric modulated arc therapy (VMAT) for multitarget stereotactic radiosurgery (SRS). METHODS AND MATERIALS This retrospective study included 50 SRS cases, each with 2 intracranial planning target volumes (PTVs). Both PTVs were planned for simultaneous treatment to 21 Gy using a single-isocenter, noncoplanar VMAT SRS technique. Rotational errors of 0.5°, 1.0°, and 2.0° were simulated about all axes. The dose to 95% of the PTV (D95) and the volume covered by 95% of the prescribed dose (V95) were evaluated using multivariate analysis to determine how PTV coverage was related to PTV volume, PTV separation, and rotational error. RESULTS At 0.5° rotational error, D95 values and V95 coverage rates were ≥95% in all cases. For rotational errors of 1.0°, 7% of targets had D95 and V95 values <95%. Coverage worsened substantially when the rotational error increased to 2.0°: D95 and V95 values were >95% for only 63% of the targets. Multivariate analysis showed that PTV volume and distance to isocenter were strong predictors of target coverage. CONCLUSIONS The effects of rotational errors on target coverage were studied across a broad range of SRS cases. In general, the risk of compromised coverage increased with decreasing target volume, increasing rotational error and increasing distance between targets. Multivariate regression models from this study may be used to quantify the dosimetric effects of rotational errors on target coverage given patient-specific input parameters of PTV volume and distance to isocenter.

Breast reconstruction and post-mastectomy radiation practice

PurposeThe goal of this study was to explore the perspectives and practice of radiation oncologists who treat breast cancer patients who have had breast reconstruction.MethodsIn 2010, an original electronic survey was sent to all physician members of the American Society of Radiation Oncology, National Cancer Research Institute-Breast Cancer Studies Group in the United Kingdom, Thai Society of Therapeutic Radiology and Oncology, Swiss Society of Radiation Oncology, and Turkish Radiation Oncology Society. We identified factors associated with radiation oncologists who treat breast cancer patients with reconstruction performed prior to radiation and obtained information regarding radiation management of the breast reconstruction.Results358 radiation oncologists responded, and 60% of the physicians were from the United States. While 64% of participants agree or strongly agree that breast image affects a woman’s quality of life during radiation, 57% feel that reconstruction challenges their ability to deliver effective breast radiation. Compared with other countries, treatment within the United States was associated with a high reconstruction rate (>/= 50% of mastectomy patients) prior to radiation (p < 0.05). Delayed-immediate reconstruction with a temporary tissue expander was more common in the United States than in other countries (52% vs. 23%, p = 0.01). Among physicians who treat patients with tissue expanders, the majority (60%) prefer a moderately inflated implant with 150-250 cc of fluid rather than a completely deflated (13%) or inflated expander (28%) during radiation. Among radiation oncologists who treat reconstructions, 49% never use bolus and 40% never boost a breast reconstruction. United States physicians were more likely than physicians from other countries to boost or bolus the reconstruction irrespective of the type of reconstruction seen in their clinic patients (p < 0.01).ConclusionsGreat variation in practice is evident from our study of radiation treatment for breast cancer patients with reconstruction. Further research on the impact and delivery of radiation to a reconstructed breast may validate some of the observed practices, highlight the variability in treatment practice, and help create a treatment consensus.

Poly (ADP) ribose polymerase enzyme inhibitor, veliparib, potentiates chemotherapy and radiation in vitro and in vivo in small cell lung cancer.

Poly (ADP) ribose polymerase (PARP) plays a key role in DNA repair and is highly expressed in small cell lung cancer (SCLC). We investigated the therapeutic impact of PARP inhibition in SCLC. In vitro cytotoxicity of veliparib, cisplatin, carboplatin, and etoposide singly and combined was determined by MTS in 9 SCLC cell lines (H69, H128, H146, H526, H187, H209, DMS53, DMS153, and DMS114). Subcutaneous xenografts in athymic nu/nu mice of H146 and H128 cells with relatively high and low platinum sensitivity, respectively, were employed for in vivo testing. Mechanisms of differential sensitivity of SCLC cell lines to PARP inhibition were investigated by comparing protein and gene expression profiles of the platinum sensitive and the less sensitive cell lines. Veliparib showed limited single‐agent cytotoxicity but selectively potentiated (≥50% reduction in IC50) cisplatin, carboplatin, and etoposide in vitro in five of nine SCLC cell lines. Veliparib with cisplatin or etoposide or with both cisplatin and etoposide showed greater delay in tumor growth than chemotherapy alone in H146 but not H128 xenografts. The potentiating effect of veliparib was associated with in vitro cell line sensitivity to cisplatin (CC = 0.672; P = 0.048) and DNA‐PKcs protein modulation. Gene expression profiling identified differential expression of a 5‐gene panel (GLS, UBEC2, HACL1, MSI2, and LOC100129585) in cell lines with relatively greater sensitivity to platinum and veliparib combination. Veliparib potentiates standard cytotoxic agents against SCLC in a cell‐specific manner. This potentiation correlates with platinum sensitivity, DNA‐PKcs expression and a 5‐gene expression profile.

Residence proximity to benzene release sites is associated with increased incidence of non-Hodgkin lymphoma

An increased risk of non‐Hodgkin lymphoma (NHL) has been observed among individuals with occupational exposure to benzene, but the risk among those living near benzene release sites has not been well described.

Total Skin Electron Therapy for Cutaneous T-Cell Lymphoma Using a Modern Dual-Field Rotational Technique

PURPOSE To report our experience with rotational total skin electron irradiation (RTSEI) in cutaneous T-cell lymphoma (CTCL), and to examine response by disease stage and race. METHODS AND MATERIALS We reviewed our outcomes for 68 CTCL patients who received RTSEI (≥ 30 Gy) from 2000 to 2013. Primary outcomes were complete clinical response (CCR), recurrence-free survival (RFS), and overall survival (OS). Using log-rank tests and Cox proportional hazards, OS and RFS were compared across tumor stages at time of RTSEI with further racial subgroup analysis. RESULTS Median age at diagnosis and at time of radiation was 52 and 56 years, respectively. Median follow-up was 5.1 years, 49% were African American, and 49% were female. At time of treatment, 18, 37, and 13 patients were T stage 2, 3, and 4, respectively. At 6 weeks after RTSEI, overall CCR was 82% (88%, 83%, and 69% for T2, T3, and T4, respectively). Median RFS was 11 months for all patients and 14, 10, and 12 months for stage T2, T3, and T4, respectively. Tumor stage was not associated with RFS or CCR. Maintenance therapy after RTSEI was associated with improved RFS in both crude and multivariable analysis, controlling for T stage. Median OS was 76 months (91 and 59 months for T3 and T4, respectively). With the exception of improved OS in African Americans compared with whites at stage T2, race was not associated with CCR, RFS, or OS. CONCLUSIONS These results represent the largest RTSEI clinical outcomes study in the modern era using a dual-field rotational technique. Our observed response rates match or improve upon the standard set by previous outcome studies using conventional TSEI techniques, despite a large percentage of advanced CTCL lesions in our cohort. We found that clinical response after RTSEI did not seem to be affected by T stage or race.

Reduced acute toxicity associated with the use of volumetric modulated arc therapy for the treatment of adenocarcinoma of the prostate.

PURPOSE Novel techniques to deliver intensity modulated radiation therapy (IMRT) have resulted in improved treatment efficiency and dosimetric endpoints. We aimed to compare acute gastrointestinal (GI) and genitourinary (GU) toxicity in patients treated for adenocarcinoma of the prostate (ACP) using volumetric modulated arc therapy (VMAT). METHODS AND MATERIALS A total of 122 (71 IMRT and 51 VMAT) ACP patients treated from 2004 to 2011 with definitive external beam radiation therapy were analyzed. Dose-volume histogram endpoints (V40, V65, V70, and V75 of the bladder and rectum) were collected for each patient. Median follow-up for patients treated with VMAT was 269 days versus IMRT was 1121 days. Acute Common Toxicity Criteria for Adverse Events (CTCAE) GI and GU toxicity scores, obtained during each weekly treatment check, were compared across cohorts. The univariate (UV) association between the covariates and outcomes was assessed and multivariable (MV) cumulative logit models were fit for each outcome. RESULTS Median patient age was 68 years and median prostate-specific antigen was 8.3. Both bladder and rectal V40, V65, V70, and V75 were all higher in the IMRT group versus the VMAT group (P < .05), which was likely influenced by larger planning target volumes in the IMRT group. The VMAT group had significantly lower rates of acute GU and acute GI CTCAE toxicity on UV association analysis. On MV analysis, VMAT remained independently associated with acute GU (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.07-0.44; P < .001) and GI (OR, 0.16; 95% CI, 0.07-0.41; P < .001) toxicity. CONCLUSIONS VMAT appears to be independently associated with lower rates of acute GI and GU toxicity when compared with traditional IMRT. Further exploration of toxicity improvements associated with VMAT use in the definitive treatment of ACP is needed.

The role of radiotherapy for patients over age 60 with diffuse large B-cell lymphoma in the rituximab era

Abstract The role of consolidative radiotherapy (RT) in patients ≥60 years old with DLBCL in the rituximab era is controversial. We examined the impact on disease control and overall survival by the addition of consolidative RT after completion of chemotherapy, while adjusting for known adverse risk factors. Retrospective chart review from 2004 to 2012 of 83 consecutive patients ≥60 years old with DLBCL treated in the rituximab era, 68 of which had a complete response to chemotherapy, was performed. Amongst patients with a complete response, consolidative RT use was associated with 100% 5-year local control, improved progression-free survival (p = 0.047), and a trend for overall survival (p = .098) on multivariate analysis. Amongst all patients, the use of consolidative RT was associated with improved overall survival (p = 0.03). The use of consolidative RT should be considered for patients ≥60 years old independent of stage and response to chemotherapy.