A Pilot Study of Pembrolizumab Combined With Stereotactic Ablative Radiotherapy for Patients With Advanced or Metastatic Sarcoma.

OBJECTIVES: Immunotherapy with immune checkpoint inhibitors has shown only limited success in the management of metastatic soft tissue sarcoma. Overall response rates (ORR) with single agent pembrolizumab were 18% and median PFS was 18 weeks on the clinical trial SARC028. One strategy to improve the responses to immunotherapy is with stereotactic body radiation therapy (SBRT), which can enhance the antitumor CD8 T cell response through the release of tumor-specific antigens, potentially priming a more diverse class of T cell receptors. METHODS: This is a phase 0, pilot prospective study taking place at a single center with 2 arms. In Arm A, patients are treated with pembrolizumab 400 mg IV infusion on day 1 of a 42-day cycle. Stereotactic body radiation therapy (SBRT) is delivered in 1-5 fractions starting on C1D15-28 and given every other day. In Arm B, patients who have started an immune checkpoint inhibitor within 60 days are treated with SBRT in addition to the current therapy. RESULTS: In this study we outline testing the feasibility of adding SBRT to pembrolizumab. CONCLUSION: The ultimate goal of combination therapy is improved overall response, including tumors not treated with SBRT. This trial can be found registered online: NCT05488366.

De-Escalation Treatment for Human Papillomavirus-Related Oropharyngeal Cancer: Questions for Practical Consideration.

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC), which accounts for an increasing proportion of all head and neck cancers, represents a specific entity with distinct clinical and molecular characteristics. It is now firmly established that patients with HPV-positive oropharyngeal SCC have a significantly improved prognosis because this variant has exquisite radiosensitivity compared with HPV-negative oropharyngeal SCC; thus, it can be targeted with de-escalated approaches using reduced doses of radiation and/or chemotherapy. The overriding goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the incidence of both short- and long-term toxicity. Although the exact reason for the improved radiosensitivity of HPV-positive oropharyngeal carcinoma is unclear, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain high rates of cure and preserve the quality of life for appropriately selected patients with this disease. However, these studies have been complicated by such factors as the relatively limited sample sizes, as well as the variability in treatment, inclusion criteria, and follow-up. How treatment paradigms will evolve, particularly in the era of precision medicine, is a provocative question and is the subject of this review.

Patient-reported quality-of-life outcomes after de-escalated chemoradiation for human papillomavirus-positive oropharyngeal carcinoma: Findings from a phase 2 trial.

BACKGROUND: The current study represents a subset analysis of quality-of-life (QOL) outcomes among patients treated on a phase 2 trial of de-escalated chemoradiation for human papillomavirus (HPV)-associated oropharyngeal cancer. METHODS: Eligibility included newly diagnosed, (American Joint Committee on Cancer, 7th edition) stage III or IV oropharyngeal squamous cell carcinoma, p16 positivity, age ≥ 18 years, and a Zubrod performance status of 0 to 1. Treatment was induction paclitaxel at a dose of 175 mg/m2 and carboplatin at an area under the curve of 6 for 2 cycles followed by response-adapted, dose-reduced radiation of 54 Gy or 60 Gy with weekly concurrent paclitaxel at a dose of 30 mg/m2 . The University of Washington Quality of Life (UW-QOL) and the Functional Assessment of Cancer Therapy-Head and Neck questionnaires were used to assess patient-reported QOL as a secondary endpoint. RESULTS: A total of 45 patients were registered, 40 of whom completed QOL surveys and were evaluable. Nadirs for overall UW-QOL and Functional Assessment of Cancer Therapy-Head and Neck scores were reached at 4 weeks after treatment but returned to baseline at 3 months. Nearly all functional indices returned to baseline levels by 6 to 9 months. The mean overall UW-QOL score was 71.6 at baseline compared with 70.8, 73.0, 83.3, and 81.1, respectively, at 3 months, 6 months, 1 year, and 2 years after therapy. The percentage of patients rating their overall QOL as "very good" or "outstanding" at 6 months, 1 year, and 2 years using the UW-QOL was 50%, 77%, and 84%, respectively. CONCLUSIONS: This de-escalation regimen achieved QOL outcomes that were favorable compared with historical controls. These results serve as powerful evidence that ongoing de-escalation efforts lead to tangible gains in function and QOL. Cancer 2018;124:521-9. © 2017 American Cancer Society.

Undifferentiated Endometrial Carcinomas: Clinicopathologic Characteristics and Treatment Outcomes.

OBJECTIVE: Undifferentiated endometrial carcinoma (UEC) represents a recently recognized and rare diagnosis that is commonly misclassified on histopathologic evaluation. These cancers account for less than 10% of carefully reviewed series of endometrial cancers from academic medical centers. We reviewed a single-institutional experience with the management of UEC focusing on clinicopathologic characteristics and treatment outcomes. METHODS: The medical records of all patients treated for histologically proven endometrial carcinoma between 2007 through 2016 were reviewed. Analysis was limited to 24 consecutive patients with histologically proven endometrial carcinomas that had at least a component of undifferentiated carcinoma on central pathology review. All patients were initially treated by definitive surgical resection. Grade 3 endometrioid carcinomas treated over the same period were used as a control group. The Kaplan-Meier method was used to estimate survival outcomes. RESULTS: The median age at diagnosis was 66 years (range, 37-74 years). Ten patients presented with locally advanced or metastatic disease (42%). Fifteen patients (63%) received adjuvant chemotherapy with carboplatin and paclitaxel, 12 patients (50%) received adjuvant pelvic external beam radiation, and 10 patients (42%) received adjuvant vaginal cuff brachytherapy. With a median follow-up of 14 months (range, 0.5-115 months), 4 patients (21%) had developed disease recurrence and/or progression, 2 patients (11%) had died of disease, and 1 patient died of treatment complications. Twelve patients (63%) were alive with no evidence of disease at last contact. Outcomes were comparable to those with grade 3 endometrioid carcinoma. CONCLUSIONS: Our data are consistent with prior studies demonstrating that UEC represents a rare clinical entity characterized by high rates of locally advanced disease at presentation. However, survival outcomes appear to be comparable to other high-grade endometrial cancers. Further studies investigating optimal adjuvant therapy in these patients are warranted.

Prognostic significance of HPV status in the re-irradiation of recurrent and second primary cancers of the head and neck.

PURPOSE: To evaluate the prognostic significance of human papillomavirus (HPV) status among patients treated by salvage radiation therapy for local-regional recurrences and second primary cancers of the head and neck arising in a previously irradiated field. METHODS AND MATERIALS: The medical records of 54 consecutive patients who underwent re-irradiation for squamous cell carcinoma of the head and neck occurring in a previously irradiated field were reviewed. Only patients with biopsy-proven evidence of recurrent disease that had previously been treated with doses of radiation therapy of at least 60 Gy were included. Determination of HPV status at the time of recurrence was performed by p16 immunohistochemistry. The median age at re-irradiation was 58.5 years (range, 27.9 to 81.5 years). Thirty patients (55.5%) were lifelong never-smokers. The Kaplan Meier method was used to calculate overall survival, progression-free survival, and local-regional control, and distant metastasis-free survival with comparisons between groups performed using the log-rank test. RESULTS: HPV status among tumors that were re-irradiated was as follows: 16 positive (29.7%); 7 negative (12.9%); 31 unknown (57.4%). The median overall survival in the entire cohort was 11.7 months (range, 8 to 27 months), with the 1-year and 2-year estimates of overall survival being 47.2% and 38.4%, respectively. A statistical trend was identified favoring patients with HPV-positive cancers with respect to the endpoints of overall survival (p = 0.06) and progression-free survival (p = 0.08) after re-irradiation when compared to the HPV-negative/unknown population. There was no significant difference in distant control between the two cohorts (p = 0.40). CONCLUSIONS: The favorable prognostic significance of HPV seemingly extends to patients treated by re-irradiation suggesting that this biomarker may be useful in risk stratification in this setting.

Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study.

BACKGROUND: Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma. METHODS: We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1. Patients received two cycles of induction chemotherapy with 175 mg/m2 paclitaxel and carboplatin (target area under the curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m2 paclitaxel per week concomitantly. Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions, and those with less than partial or no responses received 60 Gy in 30 fractions. The primary endpoint was progression-free survival at 2 years, assessed in all eligible patients who completed protocol treatment. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195. FINDINGS: Between Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with a median age of 60 years (IQR 54-67). One patient did not receive treatment and 44 were included in the analysis. 24 (55%) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with less than partial responses received 60 Gy. Median follow-up was 30 months (IQR 26-37). Three (7%) patients had locoregional recurrence and one (2%) had distant metastasis; 2-year progression-free survival was 92% (95% CI 77-97). 26 (39%) of 44 patients had grade 3 adverse events, but no grade 4 events were reported. The most common grade 3 events during induction chemotherapy were leucopenia (17 [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were dysphagia (four [9%]) and mucositis (four [9%]). One (2%) of 44 patients was dependent on a gastrostomy tube at 3 months and none was dependent 6 months after treatment. INTERPRETATION: Chemoradiotherapy with radiation doses reduced by 15-20% was associated with high progression-free survival and an improved toxicity profile compared with historical regimens using standard doses. Radiotherapy de-escalation has the potential to improve the therapeutic ratio and long-term function for these patients. FUNDING: University of California.

Re-Irradiation Therapy for Locally Recurrent Head and Neck Cancer: A National Survey of Practice Patterns.

Using a customized survey consisting of two de-identified clinical scenarios with a total of 86 questions, we showed that substantial variability exists regarding recommendations for therapy of recurrent head and neck cancer. For inoperable gross recurrence arising in a previously irradiated field, recommendations were re-irradiation with curative intent (73%), re-irradiation with palliative intent (4%), chemotherapy alone (5%), and referral to tertiary center (18%). After salvage surgery, only 33% recommended adjuvant re-irradiation, with the remainder preferring observation (46%), chemotherapy alone (10%), and referral to tertiary center (11%). Significant differences were observed with respect to dose, fractionation, technique, and systemic therapy recommendations.

Prognostic significance of p16 in squamous cell carcinoma of the larynx and hypopharynx.

PURPOSE: To evaluate the prognostic significance of p16 expression among patients with squamous cell carcinoma of the larynx (LSCC) and hypopharynx (HSCC). METHODS: The medical records of all patients with locally advanced, non-metastatic LSCC/HSCC were reviewed. p16INK4A (p16) protein expression was evaluated on pathological specimens by immunohistochemistry (IHC), and the Kaplan-Meier method was used to estimate overall survival (OS) and locoregional control (LRC). In select cases, p16 expression was correlated to high-risk and low-risk HPV genotypes using in situ hybridization (ISH). RESULTS: Thirty-one patients (23 LSCC; 8 HSCC) were identified. Seventeen (54.8%) patients were p16 negative; 14 (45.2%) were p16-positive. The primary treatment modality was radiation therapy for 22 (71.0%) patients and surgery for 9 (29.0%). Nineteen (61.3%) patients were evaluated for high-risk HPV and low-risk HPV genotypes by IHC, of whom 2 (10.5%) patients were positive for high-risk HPV and 1 (5.3%) was positive for low-risk HPV. For high-risk HPV, the positive predictive value (PPV), sensitivity, and specificity of p16 was 20.0%, 100%, and 52.9%. There was no significant difference in the 2-year actuarial rates of OS (91% vs. 64%, p=0.34) or LRC (51% vs. 46%, p=0.69) between the p16-positive and p-16 negative patients. CONCLUSION: In this small cohort of 31 LSCC and HSCC patients, p16 was not a significant predictive of either LRC or OS. Furthermore, p16 was poorly correlated with HPV genotyping as identified by ISH.

Do African-American men need separate prostate cancer screening guidelines?

BACKGROUND: In 2012, the United States Preventative Services Task Force issued new guidelines recommending that male U.S. residents, irrespective of race, no longer be screened for prostate cancer. In African American men, the incidence of prostate cancer is almost 60 % higher and the mortality rate is two to three times greater than in Caucasians. The purpose of this study is to reduce African American men's prostate cancer burden by demonstrating they need separate screening guidelines. METHODS: We performed a PubMed search using the keywords: African American, Prostate cancer, Outcomes, Molecular markers, Prostate-specific Antigen velocity, PSA density, and to derive data relevant to our hypothesis. RESULTS: In our literature review, we identified several aspects of prostate cancer that are different in Caucasian and African American men. These included prostate cancer incidence and outcome, the clinical course of the disease, serum PSA levels, genetic differences, and social barriers. It's also important to note that the USPSTF guidelines were based on two studies, one of which reported that only 4 % of its participants were African American. The other did not report demographic information, but used participants from seven European countries with small African American populations. CONCLUSION: Given the above, we conclude that separate prostate cancer screening guidelines are greatly necessary to help save the lives of African Americans.

Measuring psychosocial functioning in the radiation oncology clinic: a systematic review.

BACKGROUND: This paper aimed to systematically review the (1) prevalence, (2) risk factors, (3) interventions, and (4) measurement instruments associated with psychosocial function decline in radiation therapy (RT) patients. METHODS: A MEDLINE systematic literature review was performed to identify studies monitoring psychosocial function among RT patients as a primary endpoint. RESULTS: Fifty-seven and 22 risk factors for RT-related psychosocial function decline were identified and refuted, respectively, in 93 eligible studies representing 12,808 patients. Median prevalences of psychosocial function decline prior to, during, and following RT were 20%, 36%, and 25%. Prior to RT, anxiety was more prevalent than depression (20% vs 15%), but dropped following completion of RT, whereas median depression levels remained elevated (17% vs. 27%). Of the 79 identified risk factors, 17 were reported as predictive of psychosocial decline by two or more more studies, and five had robust support: (1) physical symptoms, (2) time point during RT, (3) chemotherapy reception, (4) female gender, and (5) younger age. Three interventions were consensually reported to improve psychosocial function: psychotherapy, nursing consultation/patient education, and self-management training. Eighty-six different assessment tools were used to monitor RT-related psychosocial function decline with the Hospital Anxiety and Depression Scale (25.8%) and the psychiatric interview (22.6%) being the most utilized. The distress thermometer has been used in 5 studies (5.4%) to date. CONCLUSION: Psychosocial function declines in approximately one-third of RT patients. Anxiety can dissipate after initiation of RT, whereas depression can persist throughout and after RT. Severe physical symptoms and time-related factors most robustly predict psychosocial function decline, which can be improved by psychotherapy and interventions aimed to improve patient education.

Tobacco use among long-term survivors of head and neck cancer treated with radiation therapy.

PURPOSE: The objective of this study is to determine the prevalence of tobacco consumption (i.e., cigarette use) among survivors of head and neck cancer after treatment with radiation therapy (RT). METHODS AND MATERIALS: A longitudinal study was conducted with 230 patients previously treated with RT for squamous cell carcinoma of the head and neck. All patients were clinically without evidence of disease and had a minimum of 1 year follow-up. Patients were summarily asked about the use of tobacco products at each follow-up visit. To explore for associations between potential predictors of post-RT smoking, the Chi-square test and Spearman's correlation coefficient were employed. RESULTS: The percentage of patients who were actively smoking was 21%, 21%, and 20%, at 1, 2, and 3 years post-RT, respectively. When the analysis was limited to patients with a former smoking history (i.e., excluding all never-smokers), these percentages increased to 32%, 27%, and 25%, respectively. The intensity of smoking at follow-up ranged from one cigarette daily to 2.5 packs daily. Forty-two of 76 (55%) patients who were smoking at diagnosis were found to be smoking at 1-year follow-up compared to 7 of 154 patients who were not (p < 0.001). The only factor that significantly predicted for persistent smoking at follow-up was the presence of a preexisting psychiatric condition (most commonly, a mood disorder) at initial cancer diagnosis. CONCLUSIONS: A significant proportion of former smokers are actively smoking during follow-up despite having completed intensive RT and having their cancers evidently under control. Innovative interventional approaches to target those at highest risk for continued smoking are warranted.

De-escalated radiation for human papillomavirus virus-related oropharyngeal cancer: Who, why, what, where, when, how, how much and what next?

The emergence of treatment de-escalation as a feasible option for patients with newly diagnosed human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma has generated considerable excitement among both providers and patients alike. Since HPV-positive oropharyngeal carcinoma has been shown to be a unique entity with distinct clinical and molecular characteristics, the rationale for customizing treatment for patients with this disease is compelling. Indeed, evidence has accumulated demonstrating that patients with HPV-positive oropharyngeal cancer have a significantly improved prognosis as a result of their exquisite radiosensitivity compared to their HPV-negative counterparts and thus might possibly be targeted with de-escalated approaches. The fundamental goal of de-escalation is to maintain the high cure and survival rates associated with traditional approaches while reducing the intensity of treatment and thus the incidence of both short- and long-term toxicity. Given the rapidly increasing incidence of this disease, particularly among younger patients who are generally healthy, the focus on quality of life seems germane. Although the exact reason for the improved sensitivity of HPV-positive oropharyngeal carcinoma to treatment is uncertain, prospective studies have now been published demonstrating that de-escalated radiation can successfully maintain the high rates of cure and preserve quality of life for appropriately selected patients with this disease. However, these studies have been fairly heterogeneous in design, and it remains questionable how to apply their findings to real-world practice. The potential of integrating translational approaches into clinical paradigms is also just starting to become recognized. Consequently, multiple uncertainties continue to exist with respect to de-escalation for HPV-positive oropharyngeal cancer, and these questions comprise the crux of this review.

Translational risk-adapted approaches to de-escalated radiation for human papillomavirus-positive oropharyngeal cancer: Past, present, and future.

Interest in the use of de-escalated radiation to treat patients with newly diagnosed human papillomavirus (HPV)-positive oropharyngeal cancer has grown dramatically with the publication of prospective trials demonstrating the efficacy of such an approach. While the rationale for de-escalation--- namely to decrease treatment-related toxicity while maintaining the excellent rates of disease control historically observed in patients with this disease-is inherently obvious, uncertainty exists regarding how to best select patients for de-escalation. Consequently, risk-adapted strategies using a variety of translational and clinical platforms have been increasingly popularized to better refine treatment. These have integrated contemporary methods of mid-treatment response assessment using advanced technologies and molecular assays to customize the radiation dose. By monitoring the response as patients actively proceed through treatment, risk-adapted protocols have the potential to provide insight into the biological behavior of tumors and make individualized therapy possible. The purpose of this review is to summarize the evidence to date on risk-adapted approaches to de-escalated radiation-- highlighting the clinical, radiological, and biological data which may ultimately help usher the principles of precision medicine into practice for patients with HPV-positive oropharyngeal cancer.

Effect of a Same-Day-Appointment Initiative on Access-Related Benchmarks in Radiation Oncology.

PURPOSE: The timely delivery of health care is an important quality indicator that has been shown to correlate with outcomes for cancer patients. We present our single-institution experience with the implementation of a same-day-access scheduling initiative in outpatient radiation oncology. METHODS AND MATERIALS: From March 2021 to March 2023, a total of 4301 consecutive new patients referred for radiation oncology consultation were offered same-day appointments as part of a prospective pilot initiative conducted at a tertiary-based academic medical center. Descriptive statistics were used to study the effect of this initiative on access-related benchmarks compared with historical control patients referred during a preceding 24-month period. RESULTS: Among the 3414 patients scheduled, 477 (14%) opted for same-day appointments. Black, Latino, and Asian patients were significantly more likely to use same-day access versus Caucasian patients (P < .001). The same-day-access initiative increased the proportion of patients seen within 5 days from referral from 22% to 61% (P < .001). The median time from referral to consult was 12 days (range, 0-149 days) before the implementation of the same-day-access initiative compared with 3 days (range, 0-101 days) after (P < .001). The no-show rate was reduced from 15% to 7% with the initiative (P < .001). All patients who requested a same-day appointment were successfully accommodated. CONCLUSIONS: The implementation of this same-day-access initiative enhanced operational efficiency and reduced barriers to care in the outpatient setting.

Refining Target Volume Coverage After Parotidectomy for Cutaneous Squamous Cell Carcinoma: Omission of the Cervical Neck From the Radiation Field.

Purpose: For patients without pathologic evidence of cervical disease after neck dissection for cutaneous squamous cell carcinoma involving the parotid region, inclusion of the ipsilateral cervical neck in the postparotidectomy radiation volume is routinely performed. We report our experience with selective avoidance of the ipsilateral neck for patients undergoing postoperative radiation to the parotid bed. Methods and Materials: From January 2014 to December 2023, a total of 30 consecutive patients underwent postoperative radiation after parotidectomy for cutaneous squamous cell carcinoma involving the parotid area. All patients had previously had a neck dissection confirming pathologic N0 disease. Treatment was delivered using intensity modulated radiation therapy to a median dose of 60 Gy (range, 56-66 Gy). The radiation target volumes included the parotid bed only, with deliberate avoidance of the ipsilateral cervical neck. The median pathologic tumor size of the parotid tumor was 3.3 cm (range, 0.2-9.4 cm). Final pathologic evaluation showed positive microscopic margins in 8 patients (27%), perineural invasion in 17 patients (57%), and facial nerve involvement in 6 patients (20%). Results: There were no isolated nodal failures. One patient developed an ipsilateral neck recurrence approximately 8 months after completion of radiation therapy. This occurred 2 months subsequent to the development of local recurrence. The 5-year actuarial rates of local (parotid) control, neck control, and overall survival were 87%, 97%, and 76%, respectively. Conclusions: Omission of the ipsilateral neck from the parotid volume does not compromise disease control for pathologically N0 patients undergoing postoperative radiation for cutaneous squamous cell carcinoma involving the parotid region. Practical implications are discussed.

Re-irradiation versus systemic therapy for the management of local-regionally recurrent head and neck cancer.

PURPOSE: The optimal management of local-regionally recurrent head and neck cancer that is not amenable to surgical resection is uncertain. We sought to compare outcomes among patients treated with and without re-irradiation in this setting. METHODS AND MATERIALS: A review of institutional registries identified 65 patients with local-regionally recurrent squamous cell carcinoma of the head and neck who were ineligible for surgery. Forty patients (62 %) opted for re-irradiation with the remaining 25 patients (38 %) undergoing initial systemic therapy alone. All patients had measurable disease. Forty-three patients (66 %) were male and twenty-two (33 %) were female. The median age at the time of recurrence was 59 years (range, 39-84 years). The most common primary sites of disease were the oropharynx, (n = 25), oral cavity (N = 19), and nasopharynx (n = 11). The median interval from completion of prior radiation to the diagnosis of recurrent disease was 35 months (range, 2-102 months). RESULTS: Re-irradiation improved 2-year overall survival, (32 % versus 11 %), progression-free survival (31 % versus 7 %), and local-regional control (39 % versus 3 %) compared to systemic therapy alone (p < 0.05, for both). The likelihood of developing any new grade 3+ toxicity was significantly higher among patients treated by re-irradiation compared to those treated by systemic therapy (53 % vs. 28 %, p < 0.001). There were 3 treatment-related fatalities, all of which occurred in the re-irradiation group. The incidence of grade 3+ late toxicity was 48 % and 12 % for patients in the re-irradiation and systemic therapy cohorts, respectively (p < 0.001). CONCLUSION: Although re-irradiation improved overall survival compared to systemic therapy for appropriately selected patients with local-regionally recurrent head and neck cancer, the relatively high risk of toxicity must be considered.

Integrating Overall Survival and Tumor Control Probability Models to Predict Local Progression After Brain Metastasis Radiosurgery.

Purpose: Stereotactic radiosurgery (SRS) for brain metastases is frequently prescribed to the maximum tolerated dose to minimize the probability of local progression. However, many patients die from extracranial disease prior to local progression and may not require maximally aggressive treatment. Recently, improvements in models of SRS tumor control probability (TCP) and overall survival (OS) have been made. We predicted that by combining models of OS and TCP, we could better predict the true risk of local progression after SRS than by using TCP modeling alone. Methods and Materials: Records of patients undergoing SRS at a single institution were reviewed retrospectively. Using established TCP and OS models, for each patient, the probability of 1-year survival [p(OS)] was calculated, as was the probability of 1-year local progression [p(LP)]) for each treated lesion. Joint-probability was used to combine the models [p(LP,OS)=p(LP)*p(OS)]. Analyses were conducted at the individual metastasis and whole-patient levels. Fine-Gray regression was used to model p(LP) or p(LP,OS) on the risk of local progression after SRS, with death as a competing risk. Results: At the patient level, 1-year local progression was 0.08 (95% CI, 0.03-0.15), median p(LP,OS) was 0.13 (95% CI, 0.07-0.2), and median p(LP) was 0.29 (95% CI, 0.22-0.38). At the metastasis level, 1-year local progression was 0.02 (95% CI, 0.01-0.04), median p(LP,OS) was 0.05 (95% CI, 0.02-0.07), and median p(LP) was 0.10 (95% CI, 0.07-0.13). p(LP,OS) was found to be significantly associated with the risk of local progression at the patient level (P = .048) and metastasis level (P = .007); however, p(LP) was not (P = .16 and P = .28, respectively). Conclusions: Simultaneous modeling of OS and TCP more accurately predicted local progression than TCP modeling alone. Better understanding which patients with brain metastases are at risk of local progression after SRS may help personalize treatment to minimize risk without sacrificing efficacy.

Correlation of radiation treatment interruptions with psychiatric disease and performance status in head and neck cancer patients.

PURPOSE: The purpose of this study is to identify factors predictive of treatment interruptions during radiation therapy (RT) for head and neck cancer. METHODS AND MATERIALS: The medical records of 280 consecutive patients who completed a 6- or 7-week course of RT for squamous cell carcinoma of the head and neck were reviewed. The number of missed treatment days, excluding those due to holidays or machine downtime, was determined for each patient. All patients were treated to a median dose of 63 Gy (range, 60 to 70 Gy). RESULTS: The proportion of patients who missed 0, 3-5, 6-10, and greater than 10 days was 25, 59, 12, and 5 %, respectively. The percentage of patients who missed greater than 5 days was 62 % among the 39 patients with Karnofsky Performance Status (KPS) score of 70 or less compared to 10 % among those with a KPS score of greater than 70 (p < 0.01). Among the 33 patients identified with a preexisting psychiatric condition, the percentage that subsequently missed greater than 5 days of treatment was 48 % compared to 13 % among those without a psychiatric condition. When missed RT days were analyzed as a continuous variable, the correlations with both KPS and preexisting psychiatric condition remained highly significant (p < 0.01, for both). CONCLUSION: Poor performance status and preexisting psychiatric condition predicted for treatment interruptions during RT for head and neck cancer. In view of the possible detrimental effect on treatment outcome, appropriate social programs should be initiated to overcome potential barriers to RT for these particular populations.

Feasibility and toxicity of concurrent chemoradiation for elderly patients with head and neck cancer.

OBJECTIVES: Although concurrent chemoradiation is increasingly used for patients with locally advanced head and neck cancer, many elderly patients receive radiation alone due to toxicity concerns. We evaluate acute and late toxicity among patients age ≥ 65 who received concurrent chemoradiation for head and neck cancer. DESIGN: Retrospective review. SETTING: Tertiary care center. PARTICIPANTS: Between 6/2003 and 8/2011, 40 consecutive patients age ≥ 65 underwent combined chemoradiation for head and neck cancer. Ten patients were treated in the postoperative setting and 30 underwent definitive chemoradiation. Twenty-eight patients received concurrent platinum-based chemotherapy and 12 received concurrent weekly paclitaxel. Treatment plans were designed to provide a dose of 66-72 Gy at 2-2.12 Gy/fraction to >95% of the gross tumor volume in the definitive setting or for positive margins and 60-66 Gy at 2 Gy/fraction post-operatively. Median follow-up was 23.2 months (range: 0-94.4 months). MAIN OUTCOMES MEASURES: Acute skin and mucosal toxicity, unplanned treatment interruptions, and chronic treatment related toxicity including gastrostomy tube dependence as graded by the CTCAE v3.0. RESULTS: Eight patients (20%) required a radiation treatment break of ≥ 3 days. Thirteen (33%) required unplanned hospitalization during or immediately following treatment. No grade 4+ skin or mucosal toxicity was noted. Five patients remained PEG tube dependent at >1 year. One patient developed non-healing mandibular osteoradionecrosis >3 years following chemoradiation. The 2-year Kaplan-Meier estimate of overall survival was 55%. CONCLUSION: Higher-than-expected rates of in-patient hospitalization with significant acute toxicity were noted in this cohort with a correspondingly high rate of radiation treatment breaks. Late toxicity rates were similar to those observed in historical controls with younger patients. Careful patient selection criteria should be employed for elderly patients considering concurrent chemoradiation for head and neck cancer.

Improved clinical outcomes with multi-modality therapy for sinonasal undifferentiated carcinoma of the head and neck.

OBJECTIVE: To examine outcomes among patients treated for sinonasal undifferentiated carcinoma (SNUC) of the head and neck. STUDY DESIGN: Retrospective review. METHODS: The records of 16 consecutive patients with newly diagnosed, non-metastatic SNUC were analyzed. Initial treatment consisted of: surgery alone (6 patients), surgery with post-operative chemoradiotherapy (4 patients), and primary radiation therapy with concurrent chemotherapy (6 patients). RESULTS: The median survival for patients treated by surgery followed by postoperative chemoradiotherapy was 30 months compared to 7 months and 9 months for patients treated by surgery alone and upfront chemoradiotherapy, respectively (p=0.20). The 2-year locoregional control was 18% for patients treated with upfront chemoradiotherapy, 37% for patients treated with surgery alone, and 78% for patients treated with surgery plus chemoradiotherapy (p=0.49). CONCLUSION: While the potential role of selection bias must be considered, multi-modality therapy using surgery and post-operative chemoradiotherapy yielded the most favorable outcomes for SNUC and should be recommended whenever feasible.