Concurrent Radiotherapy With Cetuximab or Platinum-based Chemotherapy for Locally Advanced Cutaneous Squamous Cell Carcinoma of the Head and Neck.

OBJECTIVES: The management of high-risk cutaneous squamous cell carcinoma of the head and neck (SCCHN) is not well defined. We review outcomes in patients with locally advanced cutaneous SCCHN treated with radiation and concomitant platinum (Pt)-based chemotherapy or cetuximab (Cx). METHODS: We identified 23 patients treated at our institution from 2007 to 2014. Systemic therapy consisted of Pt-based chemotherapy for 15 (65%) patients and Cx for 8 (35%) patients. Treatment intent was definitive for 48% and adjuvant for 52% of the cases. RESULTS: The majority (87%) of patients had stage III/IV disease and 9 (39%) patients had unresectable disease. All patients were being treated for recurrent disease. Aside from median age (59 Pt vs. 71 Cx, P=0.04), there were no significant differences in patient and tumor characteristics between those receiving Pt versus Cx therapy. At mean follow-up of 24 months, locoregional recurrence and distant failure were observed in 52% and 17% of all patients, respectively. Estimated 2-year disease-free survival and overall survival in the Cx versus Pt groups were: 50% versus 30% (P=0.25), and 73% versus 40% (P=0.32), respectively. CONCLUSIONS: Radiotherapy with either concurrent Pt or Cx appears to offer similar clinical outcomes in patients with locally advanced cutaneous SCCHN.

Radiotherapy for brain metastases near the end of life in an integrated health care system.

BACKGROUND: To examine radiotherapy (RT) patterns-of-care and utilization at the end of life (EOL) among non-small cell lung cancer (NSCLC) patients with brain metastasis (BrM) in an integrated health care system. METHODS: Central tumor registry identified 5,133 patients diagnosed with NSCLC from 2007-2011. BrM were determined by imaging. Patient and clinical characteristics were obtained by chart abstraction. In addition to abstracted variables, graded prognostic assessment (GPA) score of 0-1 was derived by collected data and tested as a predictor of death within 14 or 30 days of RT. RESULTS: On NSCLC presentation, 10% harbored BrM while 7% developed BrM thereafter. Of 900 BrM patients, 15% were not referred for RT, with median time to death of 21 days. Median time to death for 5% not recommended RT was 48 days. Among those receiving brain RT, 11.9% died within 14 days and 23.3% (cumulatively) died within 30 days of treatment. Over 50% with GPA score 0-1 received RT, 11% within 14 days and 21% within 30 days of death; median survival of GPA score 0-1 patients was 49 days. GPA score 0-1 independently predicted for death within 30 days of RT receipt. CONCLUSIONS: BrM are common in NSCLC, and most patients are referred for brain RT. A surprising proportion of patients received treatment near the EOL, as 23% died within 30 days of RT. GPA score of 0-1 predicted for death within 30 days of treatment. RT referral, recommendation, and timing should be better tailored to life expectancy, and additional benchmarks for quality of care are needed.

Comparison of Toxicity and Treatment Outcomes in HIV-positive Versus HIV-negative Patients With Squamous Cell Carcinoma of the Anal Canal.

PURPOSE: To compare the toxicity and treatment outcomes in human immunodeficiency virus (HIV)-positive versus HIV-negative patients with squamous cell carcinoma of the anal canal who underwent definitive concurrent chemoradiation at a single institution. MATERIALS AND METHODS: Fifty-three consecutive HIV-positive patients treated between 1987 and 2013 were compared with 205 consecutive HIV-negative patients treated between 2003 and 2013. All patients received radiotherapy at a single regional facility. The median radiation dose was 54 Gy (range, 28 to 60 Gy). Concurrent chemotherapy consisted of 2 cycles 5-FU with mitomycin-C given on day 1±day 29). After treatment, patients were closely followed with imaging studies, clinical examinations, and rigid proctoscopies. Outcomes assessed were toxicity rates, progression-free survival, colostomy-free survival, cancer-specific survival, and overall survival. RESULTS: Median follow-up was 34 months. Compared with HIV-negative patients, HIV-positive patients were younger (median age, 48 vs. 62 y) and predominantly male sex (98% of HIV-positive patients were male vs. 22% of HIV-negative patients). Of the HIV-positive patients, 37 (70%) were on highly active antiretroviral therapy, 26 (65%) had an undetectable viral load at the time of treatment, and 36 (72%) had a CD4 count>200 (mean CD4 count, 455). There were no significant differences in acute or late nonhematologic or hematologic toxicity rates between the 2 groups. At 3 years, there was no significant difference between HIV-positive and HIV-negative patients in regards to progression-free survival (75% vs. 76%), colostomy-free survival (85% vs. 85%), or cancer-specific survival (79% vs. 88%, P=0.36), respectively. On univariate analysis, there was a trend toward worse overall survival in HIV-positive patients (72% vs. 84% at 3 y, P=0.06). For the entire cohort, on multivariate analysis only male sex and stage were predictive of worse survival outcomes. HIV status was not associated with worse outcomes in Cox models. CONCLUSIONS: In the highly active antiretroviral therapy era, HIV-positive patients with anal cancer treated with standard definitive chemoradiation have equivalent toxicity and cancer-specific survival compared with HIV-negative patients.

Posttreatment FDG-PET-CT response is predictive of tumor progression and survival in anal carcinoma.

PURPOSE: We hypothesize that posttreatment F-18 fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) metabolic response predicts clinical outcomes in patients with anal cancer treated with chemoradiation. METHODS AND MATERIALS: This was a single-institution retrospective review of 148 patients treated definitively for anal squamous cell carcinoma between 2005 and 2012. All patients were followed with posttreatment PET-CT scans and clinical examinations. Progression-free survival (PFS), cause-specific survival, and overall survival (OS) estimates were calculated using the Kaplan-Meier method. RESULTS: The median follow-up was 34 months (range, 5-89 months). Pretreatment PET was successful in detecting the primary tumor in 140 cases (95%). Computed tomography (CT) alone was able to detect primary tumors in 78 of 122 patients who had pretreatment CT scans (64%). Inguinal or pelvic lymph nodes were FDG avid in 68 patients, with only 41 of these patients having enlarged lymph nodes by CT criteria (60.3%). Initial posttreatment PET-CT was obtained on average 12.7 ± 4.3 weeks after the last day of radiation (range, 5-25 weeks). Overall complete metabolic response (CR) on initial PET-CT was found in 82 patients (58%). Partial metabolic response was noted in 52 (36.9%) and progression in 7 patients (5%). Only 12/82 patients (14.6%) with a FDG-PET CR eventually recurred. The negative predictive value of a PET-CT scan performed between 13 and 25 weeks posttreatment was 92.9%. The 2-year PFS for patients with CR versus non-CR was 89.8% and 69.2%, respectively (P = .004). The 2-year OS for CR versus non-CR patients was 94.8% and 79.3% (P = .036). CONCLUSIONS: Complete metabolic response on posttreatment FDG PET-CT is highly predictive of increased PFS and OS in patients treated with chemoradiation for anal carcinoma. In addition to close clinical surveillance, we recommend obtaining posttreatment PET-CT scans >12 weeks following definitive treatment for anal cancer.

Chemoradiotherapy for squamous cell carcinoma of the anal canal: Comparison of one versus two cycles mitomycin-C.

BACKGROUND AND PURPOSE: Concurrent chemoradiotherapy with 5-fluorouracil (5-FU) and mitomycin-C (MMC) is standard treatment for anal cancer. Randomized clinical trials in Europe have used 1 cycle MMC, while North American studies use 2 cycles. We compared treatment outcomes between patients treated with either 1 or 2 cycles of concurrent MMC. MATERIAL AND METHODS: 217 consecutive patients were treated definitively with chemoradiation from 2004 to 2012 in an integrated health system. Concurrent chemotherapy regimen depended on individual practice, and consisted of 2 cycles 5-FU (1000 mg/m(2)/day on days 1-4 and 29-32), along with MMC (10-15 mg/m(2)), given on either day 1 alone (n = 154), or days 1 and 29 (n = 63). Outcomes included progression-free (PFS), cancer-specific (CSS), overall (OS), and colostomy-free survival (CFS), as well as toxicity criteria. RESULTS: Median age 60 years, 70% female, 52% T3-T4, and 40% node-positive. Median follow-up 26 months. At 2 years, outcomes were: PFS 80%, CSS 89%, OS 86%, and CFS 88%. There was no difference in PFS (HR 0.85, 95% CI 0.37-1.92), CSS (HR 0.32, 95% CI 0.07-1.42), OS (HR 0.67, 95% CI 0.25-1.83), or CFS (HR 0.91, 95% CI 0.31-2.67) between the MMC1 and MMC2 groups. Stage and male gender were predictive of worse outcomes. Acute grade ⩾ 2 toxicities were worse in the MMC2 group. There were 3 treatment-related deaths, all in the MMC2 group. CONCLUSIONS: This study suggests that MMC1 is efficacious and may be an alternative to MMC2 in patients with anal cancer treated with definitive chemoradiation, with the potential for less acute treatment-related toxicity. Randomized trials comparing these two regimens could be considered.

Elderly patients with glioblastoma multiforme treated with concurrent temozolomide and standard- versus abbreviated-course radiotherapy.

CONTEXT: Glioblastoma multiforme (GBM) is an aggressive neoplasm, with controversy regarding treatment in elderly patients. OBJECTIVE: To review outcomes of elderly patients aged ≥ 65 with newly diagnosed GBM treated with concurrent temozolomide and either standard-course radiotherapy (SRT) or abbreviated-course radiotherapy (ART). DESIGN: Retrospective review from 2003 to 2012. MAIN OUTCOME MEASURE: Survival, comparing treatment regimens. One hundred patients received SRT (median dose = 60 Gy), and 29 received ART (median dose = 35 Gy). O6- methylguanine-DNA methyltransferase (MGMT) status was available for 26 SRT and 13 ART recipients. RESULTS: Median age was 70 years. Median follow-up was 11 months. At analysis, 3 patients were alive. Multivariate analysis of the entire cohort found SRT (hazard ratio [HR] = 0.421, p = 0.0001), Karnofsky Performance Score of 70 or higher (HR = 1.894, p = 0.0031), and more extensive surgery (HR = 0.466, p = 0.0023) were associated with longer survival time, but age was not. Median time to death with SRT was 13 months versus 5.4 months with ART, but the latter had worse prognostic factors, including lower Karnofsky Performance Scores, fewer gross total resections, and higher recursive partitioning analysis class. Recipients of SRT with methylated MGMT promoter had a trend toward longer survival compared with unmethylated MGMT (p = 0.06), but ART recipients had shorter survival with MGMT methylation (p = 0.02). CONCLUSION: Elderly patients with multiple poor prognostic factors given ART had short survival times. Relative to other variables, MGMT status may not predict outcome for these patients.

Parathyroid hormone-related protein expression is correlated with clinical course in patients with glial tumors.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) expression modulates cell survival in a number of human solid tumors. Although PTHrP is expressed in normal developing and neoplastic central nervous system tissue, clinical data indicating the importance of this protein with respect to local control and/or survival in patients with glial tumors are scarce. METHODS: Using a standard immunoperoxidase technique, the authors examined PTHrP expression in a population of 51 patients with Daumas-Duport Grade II-IV astrocytomas over a 15-year period. Both local control and survival were calculated from the date of definitive irradiation to the last time of known follow-up examination using the actuarial method. PTHrP expression was scored on examination under 40x magnification, with the incidence of cellular staining averaged over 10 high-power fields. The intensity and extent of staining were characterized semiquantitatively using the standard World Health Organization classification criteria. The median follow-up duration was approximately 5.5 years. Multivariate analyses were performed to ascertain the statistical significance of several standard clinicohistopatholgic factors (Karnofsky functional status, age, gender, extent of surgical resection, radiotherapy dose, grade, and PTHrP expression) with respect to local control and survival. P < 0.05 was considered indicative of statistical significance. RESULTS: Patients with high levels of PTHrP expression had significantly lower glial tumor local control rates and corresponding decreases in progression-free and overall actuarial survival after definitive irradiation (P < 0.01). In a Cox 3-variable model, the PTHrP staining score was independent of tumor grade or Karnofsky functional status. It is notable that the strongest predictor of survival was tumor grade (P < 0.001). CONCLUSIONS: PTHrP may be an important adjunct to standard immunopathologic criteria in the determination of glial tumor responses. A number of mechanisms were explored to derive a more mechanistic understanding of these translational results. Subsequent prospective studies involving larger patient populations will be necessary before findings can be translated to clinical practice.

Noninvasive estimation of the pressure gradient across stenoses using sonographic contrast: in vitro validation.

OBJECTIVE: Because velocity measurements to estimate the degree of arterial stenosis are susceptible to local and systemic factors, we aimed to investigate the feasibility of estimating the pressure gradient across a stenosis noninvasively by using sonographic contrast. METHODS: Using a gravity-fed flow system, a 1:4000 dilution of a contrast agent in water was circulated through silicone tubes that had either focal or long-segment stenoses of varying severity in a water bath. We measured the cross-sectional areas of the normal and stenotic regions with B-mode sonography and the flow velocity with spectral Doppler sonography and calculated the pressure gradients across the stenoses using the empirically derived Young mathematical model and the simplified Bernoulli equation. Estimated gradients were compared with those measured manometerically. RESULTS: Both methods yielded estimates of pressure gradients that correlated with measured gradients (r > 0.988). In focal and long-segment stenoses, the Young model yielded gradients that agreed more closely with manometerically measured values than the Bernoulli equation (+/- 8% versus -24%-57%). Both methods were highly dependent on the ability to measure the luminal cross-sectional area. The presence of sonographic contrast in the vascular lumen highlighted the inner wall, allowing the accurate measurement of the luminal area to +/- 3.0%. CONCLUSIONS: The pressure gradient can be estimated across stenoses noninvasively. The Young model was more accurate than the simplified Bernoulli equation in this model using steady flow. Estimated gradients are highly dependent on the definition of the vascular lumen, a process aided by the use of sonographic contrast.