Scott M. Glaser

Anaplastic thyroid cancer: Prognostic factors, patterns of care, and overall survival

Anaplastic thyroid cancer (ATC) represents a rare, aggressive malignancy. We analyzed factors predictive for overall survival (OS) and treatment modality utilization.

Confirmation of proposed human papillomavirus risk-adapted staging according to AJCC/UICC TNM criteria for positive oropharyngeal carcinomas.

Patients with human papillomavirus (HPV)–related oropharyngeal cancers (OPCs) have superior outcomes in comparison with patients with non–HPV‐induced OPCs. This study confirms that a previously proposed HPV risk–adapted restaging system better reflects disease outcomes.

The impact of the omission or inadequate dosing of radiotherapy in extranodal natural killer T-cell lymphoma, nasal type, in the United States: Treatment Selection for NK T-Cell Lymphoma

Extranodal natural killer T‐cell lymphoma, nasal‐type (NKTCL), is a rare malignancy in Western populations and is thus challenging for standardization of care and a prospective study. This study was aimed at defining patterns of care for NKTCL in the context of radiotherapy (RT) use and dose selection in the United States.

Surveillance and Radiation Therapy for Stage I Seminoma—Have We Learned From the Evidence?

PURPOSE To analyze, in the setting of stage I seminoma, the factors affecting adjuvant treatment decisions and resulting survival outcomes, using a national dataset. METHODS AND MATERIALS We identified 33,094 stage I seminoma patients after orchiectomy from 1998 to 2012 from the National Cancer Data Base. Factors affecting treatment selection (active surveillance [AS] vs adjuvant treatment [AT]) were identified using a parsimonious multivariate logistic regression model. Propensity scores for treatment decision were generated and incorporated into a multivariate Cox regression analysis of overall survival. This process was then repeated within the AT cohort for factors predictive for chemotherapy [CT] versus radiation therapy [RT]. RESULTS Only 33% of patients received AS, and 65% received AT (89% RT and 11% CT). From 1998 to 2012 the proportion receiving AS increased from 23% to 60%, whereas RT utilization decreased from 73% to 21%, and CT utilization increased from 2% to 17%. Utilization of low-dose RT increased from 1.5% in 1999 to 34% in 2012. There was a small absolute overall survival advantage to AT over AS at 10 years (95.0% vs 93.4%, propensity adjusted hazard ratio 0.58, P<.0005). CONCLUSIONS There has been a significant increase in use of AS for stage I seminoma, influenced by both sociodemogrpahic and clinicopathologic factors. Between AT options, there has been significant increase in use of CT, mirrored by a decline in use of RT. Although overall survival remains high for all 3 treatment strategies, AT seems to be associated with a small absolute survival advantage over AS up to 10 years out from diagnosis.

Brachytherapy for malignancies of the vagina in the 3D era

Vaginal cancer is an uncommon malignancy and can be either recurrent or primary. In both cases, brachytherapy places a central role in the overall treatment course. Recent technological advances have led to more advanced brachytherapy techniques, which in turn have translated to improved outcomes for patients with malignancies of the vagina. The aim of this manuscript is to outline the incorporation of modern brachytherapy into the treatment of patients with vaginal cancer including patient selection along with the role of brachytherapy in conjunction with other treatment modalities, various brachytherapy techniques, treatment planning, dose fractionation schedules, and normal tissue tolerance.

Results of a Single Institution Experience with Dose-Escalated Chemoradiation for Locally Advanced Unresectable Non-Small Cell Lung Cancer

Background We determined factors associated with morbidity and outcomes of a series of non-small cell lung cancer (NSCLC) patients treated with dose-escalated chemoradiotherapy at the University of Pittsburgh Lung Cancer Program. Methods and materials The records of 170 stage III NSCLC patients treated with definitive intent were retrospectively reviewed. All patients received four-dimensional CT simulation scan and had respiratory gating if tumor movement exceeded 5 mm. Overall survival (OS), locoregional control (LRC), and freedom from distant metastasis (FFDM) were calculated using log-rank and Cox regression analysis. Results For the present series of patients, median follow-up was 36.6 months, median survival 27.4 months, and the 2- and 4-year OS was 56.0 and 30.7%, respectively. The 4-year LRC and FFDM were 43.9 and 40.7%, respectively. No benefit was associated with irradiation doses above 66 Gy in OS (p = 0.586), LRC (p = 0.440), or FFDM (p = 0.230). On univariate analysis, variables associated with worse survival included: clinical stage IIIB (p = 0.037), planning target volume (PTV) over 450 cc (p < 0.001), heart V30 over 40% (p = −0.048), and esophageal mean dose over 20% (p = 0.024), V5 (p = −0.015), and V60 (p = −0.011). On multivariable analysis, PTV above 450 cc (52.2 vs. 25.3 months, p < 0.001) and esophageal V60 >20% (43.8 vs. 21.3 months, p = −0.01) were associated with lower survival. Grade 2 or higher acute lung toxicity and esophagitis were detected in 9.5 and 59.7%, respectively of patients. Grade 2 or higher acute lung toxicity was reduced if lung V5 was ≤65 (7.4 vs. 23.8%, p = 0.03). Grade 2 or higher acute esophagitis was reduced if V60 ≤ 20% (62 vs. 81.3%, p = 0.018). The use of intensity-modulated radiation therapy was more frequent in stage IIIB compared to stage IIIA patients (56.5 vs. 39.5%, p = 0.048) and was associated with a higher lung V5 and V10. Conclusion The outcomes of a program of dose-escalated chemoradiotherapy for unresectable stage IIIA and IIIB NSCLC patients were consistent with other studies and showed no benefit to radiation doses above 66 Gy. Furthermore, maintaining low esophageal V60 and lung V5 were associated with lower morbidity and mortality.

Inguinal nodal region radiotherapy for vulvar cancer: Are we missing the target again?

The GROINSS-V II trial, in which NRG is also participating, is an ongoing observational study. As part of definitive therapy, patients with vulvar cancer undergo sentinel lymph node biopsy (SLNB) followed by observation if SLNB is negative or radiotherapy if SLNB is positive. Chemotherapy is at the discretion of the treating institution. Radiation is to be delivered to the bilateral inguinal nodes and the lower half of the external iliac nodes (though can be delivered only ipsilaterally at the discretion of the treating physician if the primary is well lateralized and there is no sign of a sentinel node on the contralateral side). The interim analysis of the ongoing GROINSS-V II trial showed a recurrence in 12.2% (10/82) of patients treated with radiation in the setting of positive sentinel lymph node biopsy [1]. On subset analysis the risk of nodal recurrence was 2.2% for micrometastases (≤2 mm) and 20% for macrometastases. Based on these early results, the study was modified to allow RT only for micrometastases and patients withmacrometastases now go on to receive completion inguinal dissection followed by possible adjuvant RT. When compared to single institution retrospective data for prophylactic groin RT [2,3], this failure rate appears to be on the higher side and raises the question of whether the outcomes seen in GROINSSV II speak more to the biology of disease in this group of patients or to a geographical miss with radiotherapy. When considering this, we were compelled to examine the radiation technique in this trial protocol as compared to historical techniques and current recommendations. In an early attempt to investigate the role of radiation therapy in the setting of vulvar cancer as a potentialmethod to decrease themorbidity associated with inguinal lymph node dissection, GOG 88 randomized patients with stage IB-III, cN0, vulvar cancer status post radical vulvectomy to either bilateral inguinal radiation or bilateral inguinal lymph node dissection followed by radiation to the pelvic and inguinal nodal regions if the dissection was positive [4]. This trial showed a greater number of inguinal recurrences in the radiation arm, however the radiation technique was poor and delivered an inadequate dose to the region at risk. In GOG 88 radiation was delivered without a CT scan for planning. This resulted in twodisadvantages. First, the risk of lymphnode involvement was not assessed and thus patients may indeed have had macroscopic disease for which 50 Gy is not sufficient. Second, the precise

Stereotactic body radiotherapy for locally-advanced unresectable pancreatic cancer—patterns of care and overall survival

Background Unresectable pancreatic cancer remains a challenging disease to treat. Stereotactic body radiotherapy (SBRT) allows for a higher biologically equivalent dose in an abbreviated course more convenient for patients and the integration of systemic therapy. We sought to investigate utilization trends and survival outcomes for patients treated with pancreatic SBRT versus conventionally fractionated radiotherapy (CFRT). Methods We engaged the National Cancer Database (NCDB) from 1998-2012 and identified locally-advanced unresectable patients with histologically confirmed, non-metastatic, pancreatic adenocarcinoma who received radiotherapy. Patients who received CFRT (1.5-4.0 Gy per fraction to a dose of ≥45 Gy, n=11,879) were compared to those who received SBRT (6-15 Gy per fraction to a dose of ≥20 Gy, n=474). Results Median follow-up was 11.0 months (18.4 months for survivors). SBRT utilization increased from 0.2% to 7.4% from 1998 to 2012 (P<0.05). On multivariable analysis, factors predictive for preferential utilization of SBRT over CFRT were later year of diagnosis, age ≥75 years, increased facility volume, and no chemotherapy in the initial treatment plan. Unadjusted median survival was 11.2 months for CFRT vs. 12.6 months for SBRT (P=0.002). Results were consistent in the propensity matched model. Variables predictive for improved survival on multivariable analysis were diagnosis after 2010, younger age, lower comorbidity score, tumor size <3 cm, nodal stage zero, and receipt of chemotherapy (P<0.05). Conclusions SBRT utilization has increased significantly and is associated with a small absolute improvement in overall survival (OS) compared to CFRT. The decreased treatment time, without apparent compromise in survival, makes SBRT an attractive option for patients with unresectable pancreatic cancer warranting further research.

Image-guided tandem and cylinder brachytherapy as monotherapy for definitive treatment of inoperable endometrial carcinoma

OBJECTIVES Management of endometrial cancer consists of surgical staging with adjuvant therapy guided by risk factors, though some women cannot undergo surgery due to comorbidities. We present a series of women treated with definitive high-dose rate image-guided tandem and cylinder brachytherapy (HDR-IGBT) alone. METHODS Patients with grade 1-2, clinical stage I endometrial adenocarcinoma, <50% myometrial invasion, and tumor≤2cm were reviewed. Definitive treatment consisted of 5-6 fractions HDR-IGBT alone with CT- or MRI-based planning. Local-regional control (LRC) was defined as complete imaging response and/or cessation of vaginal bleeding. RESULTS From 2007 to 2016, 45 patients were treated to a median dose of 37.5Gy. The median gross tumor volume (GTV) and clinical target volume (CTV) were 5.9cm3 (range, 0.7-18.7) and 80.9cm3 (17.2-159.0), respectively. The median cumulative dose to 90% (D90) of the GTV was 132.8Gy (76.5-295.6) equivalent 2Gy dose, and the median CTV D90 was 49.7Gy (34.5-57.2). Median follow-up among living patients was 18.6months (3.0-64.3). Cessation of vaginal bleeding occurred in 98%. Among those with post-treatment MRI (64%), complete radiographic response was demonstrated in 90%. The 2-year LRC, cancer-specific survival, and overall survival rates were 90%, 86%, and 97%, respectively. No grade 3+ acute or late toxicity was observed. CONCLUSIONS HDR-IGBT alone for treatment of early-stage, medically inoperable endometrial cancer is feasible with excellent response rates and clinical results. This approach also allows sparing of critical organs and ensures target coverage, which contributed to the low toxicity rate and high LRC in comparison with 2D point-based series.

Utilizing clinical pathways and web-based conferences to improve quality of care in a large integrated network using breast cancer radiation therapy as the model

BackgroundClinical pathways outline criteria for dose homogeneity and critical organ dosimetry. Based upon an internal audit showing suboptimal compliance with dosimetric parameters in whole breast irradiation (WBI), we conducted a mandatory web-based teaching conference for the network. This study reports the impact of this initiative on subsequent treatment plans.MethodsRadiation treatment plans were collected for the 10 most recent patients receiving WBI at 16 institutions within the UPMC Hillman Cancer Center network. Subsequently, a web-based conference was conducted to educate staff physicians, physicists, and dosimetrists with goals for dose homogeneity and critical organ dosimetry. Six months post-conference, another 10 plans were collected from each site and compared to pre-conference plans for deviations from dosimetric criteria.ResultsDose homogeneity significantly improved after the conference with breast V105% decreasing from 15.6% to 11.2% (p = 0.004) and breast V110% decreasing from 1.3% to 0.04% (p = 0.008). A higher percentage of cases were compliant with dosimetric criteria, with breast V105% > 20% decreasing from 22.5% to 7.5% of cases (p = 0.0002) and breast V110% > 0% decreasing from 13.8% to 4.4% of cases (p = 0.003).ConclusionsImplementation of a web-based teaching conference helped improve adherence to clinical pathway dosimetric guidelines for WBI. In radiation oncology networks, this may be an effective model to ensure quality in routine practice and can be extrapolated to other disease sites.