Radiation therapy for cT1-2 carcinoma of the palatine tonsil diagnosed via a simple tonsillectomy: Dosimetry and patterns of care in the IMRT era.

OBJECTIVE: Small carcinomas of the palatine tonsil are often diagnosed via simple tonsillectomy, a maneuver with non-therapeutic intent. Herein, practice patterns for this unique situation are evaluated. PATIENTS AND METHODS: A retrospective review was performed across 10 facilities to identify patients with cT1-2 squamous carcinomas of the tonsil diagnosed by simple tonsillectomy between 2010 and 2018. Patients who received curative-intent intensity modulated radiotherapy (IMRT) without additional surgery were included. Target volumes were reviewed, and cumulative incidences of local failure and severe late dysphagia were calculated. RESULTS: From 638 oropharyngeal patients, 91 were diagnosed via simple tonsillectomy. Definitive IMRT with no additional surgery to the primary site was utilized in 57, and three with gross residual disease were excluded, leaving 54 for analysis. Margins were negative in 13%, close (<5 mm) in 13%, microscopically positive in 61%, and not reported in 13%. Doses typically delivered to gross disease (68-70.2 Gy in 33-35 fx or 66 Gy/30 fx) were prescribed to the tonsil bed in 37 (69%). Sixteen patients (29%) received doses from 60 to 66 Gy (≤2 Gy/fx) and one received 50 Gy (2 Gy/fx). No local failures were observed. One late oropharyngeal soft tissue ulcer occurred, treated conservatively (grade 2). At five years, the cumulative incidence of severe late dysphagia was 17.4% (95% CI 6.1-28.8%). CONCLUSION: Small tonsil carcinomas diagnosed by simple tonsillectomy represent a niche subset with favorable oncologic outcomes. Regardless, radiation oncologists tend to deliver full-dose to the tonsil bed. The necessity of this routine could be questioned in the modern era.

Cost-Effectiveness Analysis of Ultra-Hypofractionated Whole Breast Radiation Therapy Alone Versus Hormone Therapy Alone or Combined Treatment for Low-Risk ER-Positive Early Stage Breast Cancer in Women Aged 65 Years and Older.

PURPOSE: The optimal management of early-stage, low-risk, hormone-positive breast cancer in older women remains controversial. Recent trials have shown that 5-fraction ultrahypofractionated whole-breast irradiation (U-WBI) has similar outcomes to longer courses, reducing the cost and inconvenience of treatment. We performed a cost-utility analysis to compare U-WBI to hormone therapy alone or their combination. METHODS AND MATERIALS: We simulated 3 different treatment approaches for women age 65 years or older with pT1-2N0 ER-positive invasive ductal carcinoma treated with lumpectomy with negative margins using a Markov microsimulation model. The strategies were U-WBI performed with a 3-dimensional conformal technique over 5 fractions without a boost ("radiation therapy [RT] alone"), adjuvant hormone therapy (anastrozole for 5 years) without RT ("aromatase-inhibitor [AI] alone"), or the combination of the 2. The combination strategy was calibrated to match trial results, and the relative effectiveness of the RT alone and AI alone strategies were inferred from previous randomized trials. The primary endpoint was the cost-effectiveness of the 3 strategies over a lifetime horizon as measured by the incremental cost-effectiveness ratio (ICER), with a value of $100,000/quality-adjusted life-year deemed "cost-effective." RESULTS: The model results compared with the prespecified target outcomes. On average, RT alone was the least expensive strategy ($14,775), with AI alone slightly more ($14,998), and combination therapy the costliest ($19,802). RT alone dominated AI alone (the incremental cost-effectiveness ratio [ICER] -$5089). Combination therapy, compared with RT alone, was slightly more expensive than our definition of cost-effective (ICER $113,468) but was cost-effective compared with AI alone (ICER $54,451). Probabilistic sensitivity analysis demonstrated RT alone to be cost-effective in 50% of trials, with combination therapy in 36% and AI alone in 14%. CONCLUSIONS: U-WBI alone appears the more cost-effective de-escalation strategy for these low-risk patients, compared with AI alone. Combining U-WBI and AI appears more costly but may be preferred by some patients.

An Estimate of Local Failure in the TARGIT-A Trial of Pre-pathology Intraoperative Radiation Therapy for Early Breast Cancer.

PURPOSE: TARGIT-A was a pragmatic randomized noninferiority trial including women with early-stage breast cancer treated postlumpectomy with either external beam radiation therapy (EBRT) or 50 kV x-rays delivered intraoperatively with or without EBRT, as indicated. The long-term update of the pre-pathology cohort did not include a 10-year estimate of the primary endpoint of local failure (although tabular 5-year data was provided). Here, we used the data from the pre-pathology manuscript to estimate the cumulative incidence of local failure. METHODS AND MATERIALS: Using digitizer software and the published survival curves, we extracted the Kaplan-Meier rate of local recurrence-free survival and overall survival. The extracted data were calibrated to the published point-estimates to within ±0.5%. The data were then fit to parametric survival models, and overall survival and local recurrence-free survival curves were subtracted to give the estimate of local failure in the presence of the competing risk of death. Bootstrap resampling was used to assess for parameter uncertainty in the modeling process. RESULTS: Our analysis estimated that the risk of local failure at 10 years in the TARGIT-A pre-pathology cohort is approximately 1.7% with EBRT (95% confidence interval [CI], 0%-4.3%) and 5.5% in the pragmatic risk-adapted TARGIT strategy (95% CI, 2.9%-8.0%). A weighted average estimate suggests that the risk of local failure in low-risk women treated with TARGIT alone is approximately 6.6% at 10 years (95% CI, 3.3%-10.0%), with an estimated difference of 4.9% (95% CI, 0.6%-9.2%) compared with EBRT. CONCLUSIONS: These data allow for contextualization and informed decisions when considering megavoltage EBRT, kilovoltage intraoperatively, or omission of radiation therapy entirely.

Imaging and Biomarker Surveillance for Head and Neck Squamous Cell Carcinoma: A Systematic Review and AUC Document.

Surveillance for survivors of head and neck cancer (HNC) is focused on early detection of recurrent or second primary malignancies. After initial restaging confirms disease-free status, the use of surveillance imaging for asymptomatic patients with HNC is controversial. Our objective was to comprehensively review literature pertaining to imaging and biomarker surveillance of asymptomatic patients treated for head and neck squamous cell carcinoma and to convene a multidisciplinary expert panel to provide appropriate use criteria for surveillance in representative clinical scenarios. The evidence base for the appropriate use criteria was gathered through a librarian-mediated search of literature published from 1990 to 2022 focused on surveillance imaging and circulating tumor-specific DNA for nonmetastatic head and neck squamous cell carcinoma using MEDLINE (Ovid), Embase, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials. The systematic review was reported according to PRISMA guidelines. Using the modified Delphi process, the expert panel voted on appropriate use criteria, providing recommendations for appropriate use of surveillance imaging and human papillomavirus (HPV) circulating tumor DNA. Of 5178 studies identified, 80 met inclusion criteria (5 meta-analyses/systematic reviews, 1 randomized control trial, 1 post hoc analysis, 25 prospective, and 48 retrospective cohort studies [with ≥50 patients]), reporting on 27,525 patients. No large, randomized, prospective trials examined whether asymptomatic patients who receive surveillance imaging or HPV circulating tumor DNA monitoring benefit from earlier detection of recurrence or second primary tumors in terms of disease-specific or quality-of-life outcomes. In the absence of prospective data, surveillance imaging for HNC survivors should rely on individualized recurrence-risk assessment accounting for initial disease staging, HPV disease status, and tobacco use history. There is an emerging surveillance role for circulating tumor biomarkers.

Defining targets to improve care delivery for T4 larynx squamous cell carcinoma.

Objective: United States oncology trends consistently demonstrate that nearly half of T4a larynx carcinoma patients are treated with larynx preservation, despite national guidelines favoring laryngectomy. This study identifies clinical decision-making drivers and defines patient subsets that should become targets for care improvement. Methods: Retrospective analysis of patients with cT4 squamous cell carcinoma of the larynx from US National Cancer Database 2005-2016. Demographic data and survival rates between clinical pathways were compared. Survival was estimated by Kaplan-Meier method with statistical comparisons assessed by log-rank test. Results: Of 11,556 patients with cT4 disease, laryngectomy (TL) was the initial treatment for 4627 (40%) patients. Larynx preservation via chemoradiation (CRT) occurred for 4307 patients. TL and CRT patients had similar Charlson-Deyo comorbidity indices and insurance status. TL patients had higher total tumor size, lower N3 rates and were more often seen at academic institutions (p < .0001). N0 surgery patients with adjuvant treatment demonstrated superior median survival (MS) compared to CRT (surgery + radiation MS: 69 months, surgery + chemoradiation MS: 66, CRT MS: 37.7), p < .0001. MS for N1/N2 disease patients was 56.5 months for surgery + radiation and 35.5 months for surgery + CRT, superior to CRT, MS 30.8 months, p < .0001. Tri-modality N3 patients with up front surgery had similar MS compared to CRT (surgery + chemoradiation 21.3 months vs. CRT 16.1), p = .95. Conclusion: National quality improvement initiatives are needed to promote guideline adherence and improve survival in advanced larynx cancer. Targets for such initiatives should be patients with limited or no nodal disease burden, that meet clear T4a imaging criteria. Level of Evidence: Level IV, non-randomized controlled cohort.

Survivorship Care Plans Improve the Identification of Post-radiation Hypothyroidism After Head and Neck Cancer Treatment.

BACKGROUND/AIM: Survivorship care programs (SCPs) educate patients on post-treatment side-effects, which may lead to earlier identification and mitigation of their impact. This study assessed the impact of SCP on identification and management of post-treatment hypothyroidism in a head and neck cancer population and evaluated socio-demographic factors in the effectiveness of SCPs. PATIENTS AND METHODS: A retrospective analysis was performed of sociodemographic and clinical characteristics of patients with head and neck cancer treated with radiation therapy between January 2011 and January 2019 at a large community cancer institution. Development of hypothyroidism was defined as elevated thyroid-stimulating hormone (TSH) or initiation of supplementation post-treatment. Cumulative incidence of hypothyroidism was analyzed with Gray's method. RESULTS: Of 608 patients, 483 (79%) had post-treatment TSH surveillance. A total of 203 (42%) of those patients developed hypothyroidism; 53 (11%) patients completed SCPs. The median follow-up was 1.4 (interquartile range=0.7-2.6) years with a median time until diagnosis of hypothyroidism of 1.2 (interquartile range=0.7-2.1) years. The median time to diagnosis was 12.0 months with SCP versus 14.2 months without. Race and insurance status were not associated with differences in thyroid surveillance. Patients with laryngeal cancer were at greatest risk of developing hypothyroidism (hazard ratio=1.92, confidence interval=1.44-2.56; p<0.077). Cumulative incidence of post-treatment hypothyroidism was higher in patients managed with SCP, 65.4% at 4 years, compared to those without (49.0%). Receipt of SCP was independently associated with an increased incidence of hypothyroidism detection (hazard ratio=1.51, confidence interval=1.04-2.20; p=0.030). CONCLUSION: In our experience, SCP utilization was independently associated with a diagnosis of hypothyroidism. This study supports implementation of a survivorship program for identification and management of post-treatment sequelae.

Retreatment of Recurrent or Second Primary Head and Neck Cancer After Prior Radiation: Executive Summary of the American Radium Society Appropriate Use Criteria.

Retreatment of recurrent or second primary head and neck cancers occurring in a previously irradiated field is complex. Few guidelines exist to support practice. We performed an updated literature search of peer-reviewed journals in a systematic fashion. Search terms, key questions, and associated clinical case variants were formed by panel consensus. The literature search informed the committee during a blinded vote on the appropriateness of treatment options via the modified Delphi method. The final number of citations retained for review was 274. These informed 5 key questions, which focused on patient selection, adjuvant reirradiation, definitive reirradiation, stereotactic body radiation, and reirradiation to treat nonsquamous cancer. Results of the consensus voting are presented along with discussion of the most current evidence. This provides updated evidence-based recommendations and guidelines for the retreatment of recurrent or second primary cancer of the head and neck.

The economic impact of circulating tumor-tissue modified HPV DNA for the post-treatment surveillance of HPV-driven oropharyngeal cancer: A simulation.

PURPOSE: Following treatment of HPV-driven oropharynx cancer, surveillance nasopharyngoscopy and imaging are often performed but are expensive and frequently ineffective. A novel plasma circulating tumor-tissue modified viral HPV DNA (TTMV-HPV-DNA) assay accurately detects recurrences. We modeled the cost of the new assay. METHODS: We designed and validated a partitioned survival model which replicated the results of the RTOG 1016 study and calculated cumulative surveillance costs from the payer's perspective. Two strategies were considered: a standard of routine endoscopy with imaging as needed and an alternative strategy which omitted scopes and imaging but obtained serial TTMV-HPV-DNA samples. No difference in effectiveness (QALY or LY) was assumed in the base case. A 5-year horizon was used, costs were reported in 2020 U.S. dollars discounted by 3%. Seven scenarios tested model assumptions and practice variation. Deterministic and probabilistic sensitivity analyses assessed parameter uncertainty. RESULTS: In the base case, at the list TTMV-HPV-DNA price, the cumulative cost of surveillance was $11,674 for the standard strategy and $20,756 for the TTMV-HPV-DNA strategy (+$9082 over 5 years). Probabilistic sensitivity analysis demonstrated the cost difference ranged from $4917-$12,047. The TTMV-HPV-DNA strategy was most likely to be either cost saving or cost-effective if future data demonstrate small improvements in quality or quantity of life (approximately 33 quality-adjusted life-days), if the assay reduces utilization of imaging, and if the periodicity of TTMV-HPV-DNA draws could be reduced from that on clinical trials. CONCLUSIONS: This data informs providers seeking to design more accurate, accessible, and economical post-treatment surveillance strategies.

Oncologists' Perspective on Dental Care Around the Treatment of Head and Neck Cancer: A Pattern of Practice Survey.

PURPOSE: Patients with head and neck cancer are at risk of long-term dental complications. Proper dental assessment pre- and post-treatment can improve outcomes but is logistically challenging. We surveyed oncologists to better understand their perspectives surrounding dental care in this unique population. METHODS: We surveyed oncologists at institutions associated with an ongoing national study of oral health after treatment of head and neck cancer. Seventeen questions were used to assess provider characteristics, patterns of practice, patterns of referral, barriers to referral, and willingness to apply fluoride varnish in the oncology clinic. RESULTS: Ninety-seven oncologists were invited from six institutions, of whom 40 (41%) responded. Surgeons represented 45% of the sample, followed by radiation oncologists (40%) and medical oncologists (15%). Both generalists and subspecialists were included. All practiced in a metropolitan area with an academic dental practice, and many felt that this improved access to care. Despite this, most oncologists thought that financial factors were a significant barrier to obtaining timely dental care. Most oncologists performed a dental assessment during visits. Oncologists felt qualified to identify the most significant complications of treatment, such as exposed bone, but felt underqualified to identify early changes in need of intervention. When asked if the oncology clinic could apply fluoride varnish during follow-ups, most stated that this seemed feasible but would require education and financial support. CONCLUSION: Oncologists often perform limited dental evaluations during their routine visits. Given the challenges associated with access to proper dental care for this population, these oncology visits may provide a window for preventative intervention.

Volumetric Modulated Arc Therapy (VMAT) Craniospinal Irradiation (CSI) for Children and Adults: A Practical Guide for Implementation.

PURPOSE: Volumetric modulated arc therapy (VMAT) craniospinal irradiation (CSI) has been shown to have significant dosimetric advantages compared to 3-dimensional conformal therapy but is a technically complex process. We sought to develop a guide for all aspects of the VMAT CSI process and report patient dosimetry results. METHODS AND MATERIALS: We initiated VMAT CSI in 2017 and have regularly revised our standard operating procedure for this process since then. Herein, we report a detailed template for the entire VMAT CSI process from initial patient setup and immobilization at time of computed tomography (CT) simulation to contouring and treatment planning, quality assurance, and therapy delivery. The records of 12 patients who were treated with VMAT CSI were also retrospectively reviewed. RESULTS: Patient age ranged from 2 to 59 years with 5 pediatric patients (age <18 years), 5 young adults (age 18-35 years), and 2 older adults (age >35 years). The majority of patients (67%) had medulloblastoma. CSI dose ranged from 21.6 to 36 Gy, with a median of 36 Gy. The median CSI planning target volume was 2383 cc with a median V95% of 99.8% and median 0.03 cc hotspot of 112.5%. The average V107% was 7.4% and the average conformality index was 1.01. CONCLUSIONS: VMAT CSI has potentially significant dosimetric and acute toxicity advantages compared to 3-dimensional conformal. However, proper procedures need to be in place throughout the process in order to be able to realize these potential advantages. We herein describe our detailed standard operating procedure for VMAT CSI. Recognizing the scarcity of proton beam centers in many areas, VMAT CSI represents a feasible treatment with more widespread availability.

Dissolved rubidium to strontium ratio as a conservative tracer for wastewater effluent-sourced contaminant inputs near a major urban wastewater treatment plant.

Municipal wastewater (MWW) effluent discharges can introduce contaminants to receiving waters which may have adverse impacts on local ecosystems and human health. Conservative chemical constituents specific to the MWW effluent stream can be used to quantify and trace wastewater effluent-sourced contaminant inputs. Gadolinium (Gd), a rare earth element used as a contrasting agent in medical magnetic resonance imaging, can be found in urban MWW streams. Dissolved anthropogenic Gd has been shown to be an indicator and potential conservative tracer for MWW effluent in receiving waters. Like other known MWW tracers, it can be difficult and expensive to measure. Dissolved rubidium (Rb) to strontium (Sr) ratio enrichment in biological materials such as blood and urine can lead to enriched Rb/Sr values in MWW effluent relative to natural waters. This ratio is relatively easy and inexpensive to measure and represents a promising additional indicator for MWW effluent in receiving waters in urbanized freshwater systems. In July 2015 and 2016 surface water samples were collected from sites in the tidal-fresh Potomac River in the vicinity of the Blue Plains Advanced Wastewater Treatment Plant (BPAWWTP) outfall near Washington, DC USA along with treated MWW effluent samples from the BPAWWTP. Dissolved Rb/Sr ratios were measured in these waters and compared to dissolved Gd concentrations in order to demonstrate the potential of the dissolved Rb/Sr ratio as a conservative indicator for MWW effluent. Results suggest the dissolved Rb/Sr ratio represents a simple and cost-effective indicator and conservative tracer for MWW effluent. It can be used with, or in place of, other proven tracers to investigate wastewater impacts in highly-urbanized, anthropogenically-impacted freshwater systems like the tidal fresh Potomac River and perhaps in a wider range of geologic settings than previously thought. A case study is presented as an example to demonstrate the potential of using dissolved Rb/Sr ratios to trace MWW-sourced nutrient inputs from a major WWTP like BPAWWTP to the receiving waters of tidal-fresh Potomac River.

Dosimetric Benefits of Omitting Primary Tumor Beds in Postoperative Radiotherapy After Transoral Robotic Surgery Using the Auto-Planning Technique.

INTRODUCTION: It has been suggested that post-transoral robotic surgery (post-TORS) radiotherapy (RT) might reduce the dose to organs at risk (OARs) adjacent to the primary tumor bed; however, the evidence supporting this has yet to be sufficient. This study examined the radiation dose reduction to OARs by omitting the primary tumor bed through the use of an Auto-Planning (AP)-based workflow. METHODS:  Twelve patients were identified who underwent post-TORS RT to the primary tumor bed and the unilateral/bilateral neck lymph nodes. In each patient, two treatment plans were designed: a Comprehensive (Comp)-plan treating the original planning target volume (PTV) including both the primary tumor bed and the lymph nodes, and a Neck-plan treating only the lymph nodes and omitting the primary tumor bed. Both plans were optimized using AP to ensure plan quality consistency. We compared the doses received by 95% of the primary tumor beds and lymph nodes (D95%) and our institutional dose constraints for the OARs between the Comp- and Neck-plans. Statistical analysis was performed using R Statistical Software (R Foundation for Statistical Computing, Vienna, Austria) with a two-tailed paired Wilcoxon signed-rank test. RESULTS:  All plans met target dose coverage requirements with at least 95% of the PTVs covered with the corresponding prescription doses. The primary tumor bed in the Neck-plans was spared with a significantly lower mean D95% (25.9 Gy vs. 60.0 Gy; p < 0.01; Wilcoxon test). The mean dose to the oral cavity (20.9 Gy vs. 28.1 Gy; p < 0.01) and the supraglottis (36.9 Gy vs. 28.2 Gy; p < 0.01) was significantly lower in the Neck-plans. CONCLUSION:  This study suggests that sparing the primary tumor bed during post-TORS RT offers dosimetric benefits to nearby OARs with significant dose reductions to the oral cavity and supraglottis. Further study of the clinical risks and benefits afforded by this strategy is needed.

Cost-Effectiveness Analysis of No Adjuvant Therapy Versus Partial Breast Irradiation Alone Versus Combined Treatment for Treatment of Low-Risk DCIS: A Microsimulation.

PURPOSE: Adjuvant therapy in patients with ductal carcinoma in situ who undergo partial mastectomy remains controversial, particularly for low-risk patients (60 years or older, estrogen-positive, tumor extent < 2.5 cm, grade 1 or 2, and margins ≥ 3 mm). We performed a cost-effectiveness analysis comparing three strategies: no adjuvant treatment after surgery, a five-fraction course of accelerated partial breast irradiation using intensity-modulated radiation therapy (accelerated partial breast irradiation [APBI]-alone), or APBI plus an aromatase inhibitor for 5 years. MATERIALS AND METHODS: Outcomes including local recurrence, distant metastases, and survival as well as toxicity data were modeled by a patient-level Markov microsimulation model, which were validated against trial data. Costs of treatment and possible adverse events were included from the societal perspective over a lifetime horizon, adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALYs) were calculated based on utilities extracted from the literature. RESULTS: No adjuvant therapy was the least costly approach ($5,744), followed by APBI-alone ($11,070); combined therapy was costliest ($16,052). Adjuvant therapy resulted in slightly higher QALYs (no adjuvant, 11.320; APBI-alone, 11.343; and combination, 11.381). In the base case, no treatment was the cost-effective strategy, with an incremental cost-effectiveness ratio of $239,109/QALY for APBI-alone and $171,718/QALY for combined therapy. The incremental cost-effectiveness ratio for combined therapy compared with APBI-alone was $131,949. Probabilistic sensitivity analyses found that no therapy was cost effective (defined as $100,000/QALY of lower) in 63% of trials, APBI-alone in 19%, and the combination in 18%. CONCLUSION: No adjuvant therapy represents the most cost-effective approach for postmenopausal women 60 years or older who receive partial mastectomy for low-risk ductal carcinoma in situ.

The Association Between Radiation Therapy Dose and Overall Survival in Patients With Intracranial Infiltrative Low-Grade Glioma Treated With Concurrent and/or Adjuvant Chemotherapy.

PURPOSE: Previous trials have shown no benefit for radiation therapy (RT) dose escalation when RT is given as adjuvant monotherapy for infiltrative low-grade glioma (LGG). However, the current standard of care for high-risk LGG is RT with concurrent and/or adjuvant chemotherapy. The effect of RT dose escalation on overall survival (OS) in the setting of concurrent and/or adjuvant chemotherapy is not well established. METHODS AND MATERIALS: We used the National Cancer Database to select records for adult patients with intracranial grade 2 LGG diagnosed between 2004 and 2015. Patients must have received adjuvant external beam RT with concurrent and/or adjuvant chemotherapy. RT dose level was categorized as standard (45-54 Gy) or high (>54-65 Gy). Multivariable and propensity score matched analyses were used. RESULTS: The study cohort consisted of 1043 patients, of whom 644 (62%) received standard dose (median, 54 Gy) and 399 (38%) received high-dose RT (median, 60 Gy). RT dose level was not associated with OS (hazard ratio, 1.2; P = .1) in multivariable analysis. Propensity score matching yielded 380 matched pairs (n = 760). There was no difference in OS for high-dose versus standard-dose RT in the matched cohort (5-year OS 64% vs 69%; P = .14) or in the 2 prespecified subgroups of astrocytoma histology and 1p/19q noncodeleted. CONCLUSIONS: Adjuvant RT dose escalation above 54 Gy in the setting of concurrent and/or adjuvant chemotherapy was not associated with improved OS for patients with infiltrative LGG in this National Cancer Database retrospective study. This was also true for the subgroups with less chemotherapy-sensitive disease, including astrocytoma histology and 1p/19q noncodeleted, although these analyses were limited by small size. Methods to improve OS other than RT dose escalation in the setting of concurrent and/or adjuvant chemotherapy should be considered for patients with poor-prognosis LGG.

Identifying an oligometastatic phenotype in HPV-associated oropharyngeal squamous cell cancer: Implications for clinical trial design.

OBJECTIVES: Patients with human papillomavirus (HPV) associated squamous cell carcinoma of the oropharynx (SCC-OP) have improved overall survival (OS) after distant metastasis (DM) compared to HPV negative patients. These patients may be appropriate candidates for enrollment on clinical trials evaluating the efficacy of metastasis-directed therapy (MDT). This study seeks to identify prognostic factors associated with OS after DM, which could serve as enrollment criteria for such trials. MATERIALS AND METHODS: From an IRB approved multi-institutional database, we retrospectively identified patients with HPV/p16 positive SCC-OP diagnosed between 2001 and 2018. Patterns of distant failure were assessed, including number of lesions at diagnosis and sites of involvement. The primary outcome was OS after DM. Prognostic factors for OS after DM were identified with Cox proportional hazards. Stepwise approach was used for multivariable analysis. RESULTS: We identified 621 patients with HPV-associated SCC-OP, of whom 82 (13.2%) were diagnosed with DM. Median OS after DM was 14.6 months. On multivariable analysis, smoking history and number of lesions were significantly associated with prolonged OS. Median OS after DM by smoking (never vs ever) was 37.6 vs 11.2 months (p = 0.006), and by lesion number (1 vs 2-4 vs 5 or more) was 41.2 vs 17.2 vs 10.8 months (p = 0.007). CONCLUSION: Among patients with newly diagnosed metastatic HPV-associated SCC-OP, lesion number and smoking status were associated with significantly prolonged overall survival. These factors should be incorporated into the design of clinical trials investigating the utility of MDT, with or without systemic therapy, in this population.

The effect of adjuvant radiotherapy on overall survival in adults with intracranial ependymoma.

BACKGROUND: Adult intracranial ependymoma is rare, and the role for adjuvant radiotherapy (RT) is not well defined. METHODS: We used the National Cancer Database (NCDB) to select adults (age ≥ 22 years) with grade 2 to 3 intracranial ependymoma status postresection between 2004 and 2015 and treated with adjuvant RT vs observation. Four cohorts were generated: (1) all patients, (2) grade 2 only, (3) grade 2 status post-subtotal resection only, (4) and grade 3 only. The association between adjuvant RT use and overall survival (OS) was assessed using multivariate Cox and propensity score matched analyses. RESULTS: A total of 1787 patients were included in cohort 1, of which 856 patients (48%) received adjuvant RT and 931 (52%) were observed. Approximately two-thirds of tumors were supratentorial and 80% were grade 2. Cohorts 2, 3, and 4 included 1471, 345, and 316 patients, respectively. There was no significant association between adjuvant RT use and OS in multivariate or propensity score matched analysis in any of the cohorts. Older age, male sex, urban location, higher comorbidity score, earlier year of diagnosis, and grade 3 were associated with increased risk of death. CONCLUSIONS: This large NCDB study did not demonstrate a significant association between adjuvant RT use and OS for adults with intracranial ependymoma, including for patients with grade 2 ependymoma status post-subtotal resection. The conflicting results regarding the efficacy of adjuvant RT in this patient population highlight the need for high-quality studies to guide therapy recommendations in adult ependymoma.

Cost-effectiveness analysis of endocrine therapy alone versus partial-breast irradiation alone versus combined treatment for low-risk hormone-positive early-stage breast cancer in women aged 70 years or older.

PURPOSE: We performed a cost-effectiveness analysis of three strategies for the adjuvant treatment of early breast cancer in women age 70 years or older: an aromatase inhibitor (AI-alone) for 5 years, a 5-fraction course of accelerated partial-breast irradiation using intensity-modulated radiation therapy (APBI-alone), or their combination. METHODS: We constructed a patient-level Markov microsimulation from the societal perspective. Effectiveness data (local recurrence, distant metastases, survival), and toxicity data were obtained from randomized trials when possible. Costs of side effects were included. Costs were adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALY) were calculated using utilities extracted from the literature. RESULTS: The strategy of AI-alone ($12,637) was cheaper than both APBI-alone ($13,799) and combination therapy ($18,012) in the base case. All approaches resulted in similar QALY outcomes (AI-alone 7.775; APBI-alone 7.768; combination 7.807). In the base case, AI-alone was the cost-effective strategy and dominated APBI-alone, while combined therapy was not cost-effective when compared to AI-alone ($171,451/QALY) or APBI-alone ($107,932/QALY). In probabilistic sensitivity analyses, AI-alone was cost-effective at $100,000/QALY in 50% of trials, APBI-alone in 28% and the combination in 22%. Scenario analysis demonstrated that APBI-alone was more effective than AI-alone when AI compliance was lower than 26% at 5 years. CONCLUSIONS: Based on a Markov microsimulation analysis, both AI-alone and APBI-alone are appropriate options for patients 70 years or older with early breast cancer with small cost differences noted. A prospective trial comparing the approaches is warranted.