First metatarsophalangeal joint dorsiflexion resistance in individuals with plantar fasciopathy.

INTRODUCTION: Plantar fasciopathy is a common foot-related musculoskeletal disorder. It has been hypothesized that this disorder could be linked to a dysfunctional windlass mechanism. However, no study to date has quantified this link to validate or refute this hypothesis. The first metatarsophalangeal joint (1st MPJ) dorsiflexion resistance test is a reliable test to evaluate the force required to initiate the windlass mechanism. Comparing the results of this test in individuals with and without plantar fasciopathy will allow for a better understanding of the relationship between plantar fasciopathy and the windlass mechanism. Thus, this study aimed to compare 1st MPJ dorsiflexion resistance in individuals with plantar fasciopathy and healthy controls. Additionally, this study aimed to explore the correlations between 1st MPJ dorsiflexion resistance and other commonly used foot orthopedic tests, specifically the supination resistance test and the Foot Posture Index. MATERIAL AND METHODS: Twenty participants with plantar fasciopathy and 20 healthy controls were recruited in this case-control study. First MPJ dorsiflexion resistance was quantified and compared between groups and between feet using a repeated measures ANOVA with one within-subject factor with two levels and one between-subject factor with two levels. It was also correlated with supination resistance and the Foot Posture Index. RESULTS: There were no significant differences in 1st MPJ dorsiflexion resistance between injured and healthy feet as well as control and plantar fasciopathy groups. There was a moderate to strong correlation (r = 0.674 to 0.891) between 1st MPJ dorsiflexion resistance and supination resistance in both groups. There was no significant correlation between 1st MPJ dorsiflexion resistance and the Foot Posture Index. CONCLUSIONS: The lack of alterations in 1st MPJ dorsiflexion resistance among individuals with plantar fasciopathy implies a potential need to reconsider the biomechanical model, proposing that a dysfunctional windlass mechanism is associated with the development of plantar fasciopathy, may need reconsideration.

Patient Safety and Satisfaction With Fully Remote Management of Radiation Oncology Care.

Importance: Patients of Memorial Sloan Kettering Cancer Center in New York, New York, are now offered a choice of either in-person or remote telehealth visits for radiation oncology care. However, safety and satisfaction among patients receiving treatment with fully remote physician management is unclear. Objective: To analyze patient safety and satisfaction, financial implications, and environmental consequences associated with fully remote management among a cohort of patients treated with radiotherapy. Design, Setting, and Participants: This single-institution retrospective cohort study was performed at Memorial Sloan Kettering Cancer Center, with patients treated with radiation who opted for fully remote management between October 1, 2020, and October 31, 2022. Data on patient safety events were prospectively collected with an in-house quality improvement reporting system. Patient satisfaction surveys were distributed electronically before, during, and after treatment. Patient transportation costs and environmental consequences were estimated based on differences in travel distance. Data analysis was performed from March 14 through September 19, 2023. Exposure: Radiotherapy with fully remote physician management. Main Outcomes and Measures: Satisfaction rates among patients opting for fully remote management were analyzed via surveys administered electronically after visits with clinicians. Patient safety events, defined as staff-reported actual events and near misses that had the potential to affect patient care, were reviewed. Rates and types of safety events were analyzed and compared with patients treated by onsite clinicians. Distances between patient home zip codes and treatment site locations were compared with estimated cost savings and decreased emissions. Results: This study included 2817 patients who received radiation oncology care with fully remote physician management. The median age of patients was 65 (range, 9-99) years, and more than half were men (1467 [52.1%]). Of the 764 safety events reported, 763 (99.9%) did not reach patients or caused no harm to patients. Nearly all survey respondents (451 [97.6%]) rated patient satisfaction as good to very good across all domains. For treatment with fully remote physician management, out-of-pocket cost savings totaled $612 912.71 ($466.45 per patient) and decreased carbon dioxide emissions by 174 metric tons. Conclusions and Relevance: In this study, radiation oncology care provided by fully remote clinicians was safe and feasible, with no serious patient events. High patient satisfaction, substantial cost savings, and decreased environmental consequences were observed. These findings support the continuation of a fully remote management option for select patients in the post-COVID-19 era.

Insurance Denials and Patient Treatment in a Large Academic Radiation Oncology Center.

Importance: Insurance barriers to cancer care can cause significant patient and clinician burden. Objective: To investigate the association of insurance denial with changes in technique, dose, and time to delivery of radiation oncology treatment. Design, Setting, and Participants: In this single-institution cohort analysis, data were collected from patients with payer-denied authorization for radiation therapy (RT) from November 1, 2021, to December 8, 2022. Data were analyzed from December 15, 2022, to December 31, 2023. Exposure: Insurance denial for RT. Main Outcomes and Measures: Association of these denials with changes in RT technique, dose, and time to treatment delivery was assessed using χ2 tests. Results: A total of 206 cases (118 women [57.3%]; median age, 58 [range, 26-91] years) were identified. Most insurers (199 [96.6%]) were commercial payers, while 7 (3.4%) were Medicare or Medicare Advantage. One hundred sixty-one patients (78.2%) were younger than 65 years. Of 206 cases, 127 (61.7%) were ultimately authorized without any change to the requested RT technique or prescription dose; 56 (27.2%) were authorized after modification to RT technique and/or prescription dose required by the payer. Of 21 cases with required prescription dose change, the median decrease in dose was 24.0 (range, 2.3-51.0) Gy. Of 202 cases (98.1%) with RT delivered, 72 (34.9%) were delayed for a mean (SD) of 7.8 (9.1) days and median of 5 (range, 1-49) days. Four cases (1.9%) ultimately did not receive any authorization, with 3 (1.5%) not undergoing RT, and 1 (0.5%) seeking treatment at another institution. Conclusions and Relevance: In this cohort study of patients with payer-denied cases, most insurance denials in radiation oncology were ultimately approved on appeal; however, RT technique and/or effectiveness may be compromised by payer-mandated changes. Further investigation and action to recognize the time and financial burdens on clinicians and clinical effects on patients caused by insurance denials of RT is needed.

Effect of time-of-day nivolumab and stereotactic body radiotherapy in metastatic head and neck squamous cell carcinoma: A secondary analysis of a prospective randomized trial.

BACKGROUND: Prior work documented circadian rhythm impacts on efficacy and toxicity of cancer therapies. METHODS: Secondary analysis of prospective, phase II trial of metastatic HNSCC randomized to nivolumab+/-SBRT. Used cutoffs of 1100 and 1630. Timing classified by first infusion or majority of SBRT (e.g., PM SBRT defined by two or three fractions after 1630). RESULTS: Of 62 patients, there was no significant difference in median PFS between AM nivolumab (n = 7, 175 days), PM nivolumab (n = 21, 58 days), or Mid-Day nivolumab (n = 34, 67 days; p = 0.8). There was no significant difference in median PFS with AM SBRT (n = 4, 78 days), PM SBRT (n = 13, 111 days), or Mid-Day SBRT (n = 15, 63 days; p = 0.8). There was no significant difference in Grade 3-4 toxicity or ORR. Sensitivity analyses with other timepoints were negative. CONCLUSIONS: Further work may elucidate circadian impacts on select patients, tumors, and therapies; however, we found no significant effect in this study.

Clinical Experience With an Offline Adaptive Radiation Therapy Head and Neck Program: Dosimetric Benefits and Opportunities for Patient Selection.

PURPOSE: The objective of this study was to develop a linear accelerator (LINAC)-based adaptive radiation therapy (ART) workflow for the head and neck that is informed by automated image tracking to identify major anatomic changes warranting adaptation. In this study, we report our initial clinical experience with the program and an investigation into potential trigger signals for ART. METHODS AND MATERIALS: Offline ART was systematically performed on patients receiving radiation therapy for head and neck cancer on C-arm LINACs. Adaptations were performed at a single time point during treatment with resimulation approximately 3 weeks into treatment. Throughout treatment, all patients were tracked using an automated image tracking system called the Automated Watchdog for Adaptive Radiotherapy Environment (AWARE). AWARE measures volumetric changes in gross tumor volumes (GTVs) and selected normal tissues via cone beam computed tomography scans and deformable registration. The benefit of ART was determined by comparing adaptive plan dosimetry and normal tissue complication probabilities against the initial plans recalculated on resimulation computed tomography scans. Dosimetric differences were then correlated with AWARE-measured volume changes to identify patient-specific triggers for ART. Candidate trigger variables were evaluated using receiver operator characteristic analysis. RESULTS: In total, 46 patients received ART in this study. Among these patients, we observed a significant decrease in dose to the submandibular glands (mean ± standard deviation: -219.2 ± 291.2 cGy, P < 10-5), parotids (-68.2 ± 197.7 cGy, P = .001), and oral cavity (-238.7 ± 206.7 cGy, P < 10-5) with the adaptive plan. Normal tissue complication probabilities for xerostomia computed from mean parotid doses also decreased significantly with the adaptive plans (P = .008). We also observed systematic intratreatment volume reductions (ΔV) for GTVs and normal tissues. Candidate triggers were identified that predicted significant improvement with ART, including parotid ΔV = 7%, neck ΔV = 2%, and nodal GTV ΔV = 29%. CONCLUSIONS: Systematic offline head and neck ART was successfully deployed on conventional LINACs and reduced doses to critical salivary structures and the oral cavity. Automated cone beam computed tomography tracking provided information regarding anatomic changes that may aid patient-specific triggering for ART.

Convergent evolution of BRCA2 reversion mutations under therapeutic pressure by PARP inhibition and platinum chemotherapy.

Reversion mutations that restore wild-type function of the BRCA gene have been described as a key mechanism of resistance to Poly(ADP-ribose) polymerase (PARP) inhibitor therapy in BRCA-associated cancers. Here, we report a case of a patient with metastatic castration-resistant prostate cancer (mCRPC) with a germline BRCA2 mutation who developed acquired resistance to PARP inhibition. Extensive genomic interrogation of cell-free DNA (cfDNA) and tissue at baseline, post-progression, and postmortem revealed ten unique BRCA2 reversion mutations across ten sites. While several of the reversion mutations were private to a specific site, nine out of ten tumors contained at least one mutation, suggesting a powerful clonal selection for reversion mutations in the presence of therapeutic pressure by PARP inhibition. Variable cfDNA shed was seen across tumor sites, emphasizing a potential shortcoming of cfDNA monitoring for PARPi resistance. This report provides a genomic portrait of the temporal and spatial heterogeneity of prostate cancer under the selective pressure of a PARP inhibition and exposes limitations in the current strategies for detection of reversion mutations.

Hypoxia-Directed Treatment of Human Papillomavirus-Related Oropharyngeal Carcinoma.

PURPOSE: Standard curative-intent chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are radioresistant, we posited that the aerobic state of a tumor could identify patients eligible for de-escalation of chemoradiotherapy while maintaining treatment efficacy. METHODS: We enrolled patients with HPV-related oropharyngeal carcinoma to receive de-escalated definitive chemoradiotherapy in a phase II study (ClinicalTrials.gov identifier: NCT03323463). Patients first underwent surgical removal of disease at their primary site, but not of gross disease in the neck. A baseline 18F-fluoromisonidazole positron emission tomography scan was used to measure tumor hypoxia and was repeated 1-2 weeks intratreatment. Patients with nonhypoxic tumors received 30 Gy (3 weeks) with chemotherapy, whereas those with hypoxic tumors received standard chemoradiotherapy to 70 Gy (7 weeks). The primary objective was achieving a 2-year locoregional control (LRC) of 95% with a 7% noninferiority margin. RESULTS: One hundred fifty-eight patients with T0-2/N1-N2c were enrolled, of which 152 patients were eligible for analyses. Of these, 128 patients met criteria for 30 Gy and 24 patients received 70 Gy. The 2-year LRC was 94.7% (95% CI, 89.8 to 97.7), meeting our primary objective. With a median follow-up time of 38.3 (range, 22.1-58.4) months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 100%, respectively, for the 30-Gy cohort. The 70-Gy cohort had similar 2-year PFS and OS rates at 96% and 96%, respectively. Acute grade 3-4 adverse events were more common in 70 Gy versus 30 Gy (58.3% v 32%; P = .02). Late grade 3-4 adverse events only occurred in the 70-Gy cohort, in which 4.5% complained of late dysphagia. CONCLUSION: Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas with preserved efficacy and substantially reduced toxicity that requires further investigation.

Trends in Utilization and Medicare Spending on Short-Course Radiation Therapy for Breast and Prostate Cancer: An Episode-Based Analysis From 2015 to 2019.

PURPOSE: Evidence supports the value of shorter, similarly efficacious, and potentially more cost-effective hypofractionated radiation therapy (RT) regimens in many clinical scenarios for breast cancer (BC) and prostate cancer (PC). However, practice patterns vary considerably. We used the most recent Centers for Medicare and Medicaid Services data to assess trends in RT cost and practice patterns among episodes of BC and PC. METHODS AND MATERIALS: We performed a retrospective cohort analysis of all external beam RT episodes for BC and PC from 2015 to 2019 to assess predictors of short-course RT (SCRT) use and calculated spending differences. Multivariable logistic regression defined adjusted odds ratios of receipt of SCRT over longer-course RT (LCRT) by treatment modality, age, year of diagnosis, type of practice, and the interaction between year and treatment setting. Medicare spending was evaluated using multivariable linear regression controlling for duration of RT regimen (SCRT vs LCRT) in addition to the above covariables. RESULTS: Of 143,729 BC episodes and 114,214 PC episodes, 63,623 (44.27%) and 25,955 (22.72%) were SCRT regimens, respectively. Median total spending for SCRT regimens among BC episodes was $9418 (interquartile range [IQR], $7966-$10,983) versus $13,602 (IQR, $11,814-$15,499) for LCRT. Among PC episodes, median total spending was $6924 (IQR, $4,509-$12,905) for stereotactic body RT, $18,768 (IQR, $15,421-$20,740) for moderate hypofractionation, and $27,319 (IQR, $25,446-$29,421) for LCRT. On logistic regression, receipt of SCRT was associated with older age among both BC and PC episodes as well as treatment at hospital-affiliated over freestanding sites (P < .001 for all). CONCLUSIONS: In this evaluation of BC and PC RT episodes from 2015 to 2019, we found that shorter-course RT resulted in lower costs than longer-course RT. SCRT was also more common in hospital-affiliated sites. Future research focusing on potential payment incentives encouraging SCRT when clinically appropriate in the 2 most common cancers treated with RT will be valuable as the field continues to prospectively evaluate cost-effective hypofractionation in other disease sites.

Major adverse cardiovascular events of enzalutamide versus abiraterone in prostate cancer: a retrospective cohort study.

BACKGROUND: While the cardiovascular risks of androgen receptor pathway inhibitors have been studied, they were seldom compared directly. This study compares the risks of major adverse cardiovascular events (MACE) between enzalutamide and abiraterone among prostate cancer (PCa) patients. METHODS: Adult PCa patients receiving either enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between 1 December 1999 and 31 March 2021 were identified in this retrospective cohort study. Patients who switched between enzalutamide and abiraterone, initiated abiraterone used without steroids, or experienced prior cardiac events were excluded. Patients were followed-up until 30 September 2021. The primary outcomes were MACE, a composite of stroke, myocardial infarction (MI), Heart failure (HF), or all-cause mortality and a composite of adverse cardiovascular events (CACE) not including all-cause mortality. The secondary outcomes were individual components of MACE. Inverse probability treatment weighting was used to balance covariates between treatment groups. RESULTS: In total, 1015 patients were analyzed (456 enzalutamide users and 559 abiraterone users; mean age 70.6 ± 8.8 years old) over a median follow-up duration of 11.3 (IQR: 5.3-21.3) months. Enzalutamide users had significantly lower risks of 4P-MACE (weighted hazard ratio (wHR) 0.71 [95% confidence interval (CI) 0.59-0.86], p < 0.001) and CACE (wHR 0.63 [95% CI: 0.42-0.96], p = 0.031), which remained consistent in multivariable analysis. Such an association may be stronger in patients aged ≥65 years or without diabetes mellitus and was independent of bilateral orchidectomy. Enzalutamide users also had significantly lower risks of MI (wHR 0.57 [95% CI: 0.33-0.97], p = 0.040) and all-cause mortality (wHR 0.71 [95% CI: 0.59-0.85], p < 0.001). CONCLUSION: Enzalutamide was associated with lower cardiovascular risks than abiraterone in PCa patients.

Supination resistance variations in foot and ankle musculoskeletal disorders: implications for diagnosis and customised interventions with wedged insoles.

BACKGROUND: Supination resistance is a clinical outcome that estimates the amount of external force required to supinate the foot. A greater supination resistance may indicate greater loads on structures responsible for generating internal supination moments across the subtalar joint during static and dynamic tasks. As such, greater supination resistance may be an expected finding in medial foot and ankle musculoskeletal disorders, such as plantar fasciopathy (PF) and posterior tibial tendon dysfunction (PTTD), whereas reduced supination resistance may be present in lateral ankle disorders, such as chronic ankle instability (CAI). However, no studies have yet investigated the changes in supination resistance across these foot and ankle musculoskeletal disorders. This study aimed to quantify supination resistance in individuals with PF, PTTD and CAI compared to healthy controls. Additionally, this study aimed to explore the changes in supination resistance following the simulation of varus and valgus wedges, which are commonly used interventions for these disorders. METHODS: Fourteen participants with PF, fourteen with PTTD, fourteen with CAI and fourteen healthy controls were recruited. Supination resistance was quantified on a level surface and on a 10-degree inclined surface with varus and valgus positions. RESULTS: Supination resistance was lower for the injured foot for CAI (p < 0.001) and greater for PTTD (p < 0.001) compared to the healthy foot. There was no significant between-foot difference observed for PF (p = 0.275) and controls (p = 0.970). In the injured foot, CAI exhibited lower supination resistance compared to controls (p < 0.001), PF (p = 0.012) and PTTD (p = 0.014). Regardless of the groups, supination resistance increased when tested on a surface with valgus inclination (p < 0.001) and decreased when tested on a surface with varus inclination (p < 0.001). CONCLUSIONS: Varus and valgus inclinations to the surface were effective in modifying supination resistance in PTTD and CAI, respectively. Supination resistance seemed unchanged in PF, and thus inclining the standing surface leads to greater between-feet asymmetries. This study also highlights the potential of wedged insoles as a mean to customise treatments and modify tissue stresses in these disorders. The findings contribute to the understanding of foot and ankle biomechanics and may aid in the development of more effective management and rehabilitation strategies.

Long-term Outcomes from a Phase 1 Dose Escalation Study Using Stereotactic Body Radiotherapy for Patients with Low- or Intermediate-risk Prostate Cancer.

BACKGROUND: Ultrahypofractionated stereotactic body radiation therapy (SBRT) has become a standard treatment intervention for localized prostate cancer. OBJECTIVE: To report final long-term tumor control outcomes and late gastrointestinal (GI) and genitourinary (GU) toxicities from a single-center phase 1 dose escalation study using SBRT for patients with low- or intermediate-risk prostate cancer. DESIGN, SETTING AND PARTICIPANTS: Between 2009 and 2012, 136 patients were enrolled and treated. The initial dose level was 32.5 Gy in five fractions. Doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy in five fractions delivered every other day. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was late treatment-related toxicity. Secondary endpoints included prostate-specific antigen (PSA) failure. RESULTS AND LIMITATIONS: The median follow-up was 10.5 yr for the 32.5-Gy group, 9.9 yr for the 35-Gy group, 8.2 yr for the 37.5-Gy group, and 7.3 yr for the 40-Gy group. The 8-yr cumulative incidence of PSA failure was 26% for 32.5 Gy, 15% for 35 Gy, 3.4% for 37.5 Gy, and 6.6% for 40 Gy. Higher radiation dose (37.5-40 Gy) and favorable intermediate risk (vs unfavorable intermediate risk) were associated with better PSA recurrence rates (p = 0.011 and 0.002, respectively). The 8-yr actuarial probability rates for survival free from late grade ≥2 toxicity were 94% for GI toxicity and 86% for GU toxicity. No grade 4 events were recorded. Higher dose levels were not associated with higher rates of late grade ≥2 GI (p = 0.2) or GU (p > 0.9) toxicity. CONCLUSIONS: SBRT doses ranging from 32.5 to 40 Gy were associated with low incidence of moderate or severe toxicities. Higher doses resulted in superior disease control outcomes 8 yr after treatment. PATIENT SUMMARY: We investigated the association between the radiotherapy dose used and the rate of control of prostate cancer. We found that higher doses resulted in more favorable outcomes without excess toxicity. This trial is registered on ClinicalTrials.gov as NCT00911118.

Differential use of postoperative psychosocial and physical services among older adults with head and neck cancer.

INTRODUCTION: Older adults undergoing head and neck cancer (HNC) surgery often have significant functional and mental health impairments. We examined use of postoperative physical, nutritional, and psychosocial services among a cohort of older adults with HNC comanaged by geriatricians and surgeons. MATERIALS AND METHODS: Our sample consisted of older adults who were referred to the Geriatrics Service at Memorial Sloan Kettering Cancer Center between 2015 and 2019 and took a geriatric assessment (GA) prior to undergoing HNC surgery. Physical, nutritional, and psychosocial service utilization was assessed. Physical services included a physical, occupational, or rehabilitation consult during the patient's stay. Nutritional services consisted of speech and swallow or nutritional consult. Psychosocial services consisted of psychiatry, psychology, or a social work consult. Relationships between each service use, geriatric deficits, demographic, and surgical characteristics were assessed using Wilcoxon rank-sum test or Chi-square test. RESULTS: In total, 157 patients were included, with median age of 80 and length of stay of six days. The most common GA impairments were major distress (61%), depression (59%), social activity limitation (SAL) (54%), and deficits in activities of daily living (ADL) (44%). Nutritional and physical services were used much more frequently than psychosocial services (80% and 85% vs 31%, respectively). Receipt of services was associated with longer median length of hospital stay, operation time, and greater deficits in ADLs. SAL was associated with physical and psychosocial consult and lower Timed Up and Go (TUG) score; instrumental ADL (iADL) deficits were associated with physical services; and depression and distress were associated with psychosocial services. DISCUSSION: The burden of psychosocial deficits is high among older adults with HNC. Future work is needed to understand the limited utilization of psychosocial services in this population as well as whether referral to psychosocial services can reduce the burden of these deficits.

Concurrent carboplatin and paclitaxel definitive radiation therapy for locally advanced head and neck cancer.

BACKGROUND: We report the outcomes of cisplatin-ineligible HNSCC patients treated with definitive chemoradiation and concurrent carboplatin and paclitaxel. MATERIALS AND METHODS: We included consecutive HNSCC patients treated from 2013 to 2021 that received definitive chemoradiation with carboplatin and paclitaxel. Locoregional recurrences (LRR) and distant metastases (DM) were estimated using cumulative incidence functions. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. RESULTS: Sixty-five patients were identified with median age of 71 years (range 44-85). Median radiation dose was 70 Gy and the median doses of carboplatin and paclitaxel were AUC 1 and 40 mg/m2 , respectively. At a median follow-up of 29 (range 5-91) months, the 2-year rates of LRR, DM, PFS, and OS were 8.8%, 9.4%, 72.2%, and 88.7%, respectively. In total, there were 5 LRR, 7 DM, and 12 deaths. CONCLUSIONS: Chemoradiation with carboplatin and paclitaxel is an excellent option for cisplatin-ineligible HNSCC patients.

Dosimetric Comparison of Intensity-Modulated Radiation Therapy (IMRT) and Intensity-Modulated Proton Therapy (IMPT) for a Novel Oral Tongue Avoidance Concept in Low-Risk Squamous Cell Carcinoma of the Oral Tongue.

Purpose: After adequate surgical resection, early-stage oral tongue cancer patients can harbor a low risk of local recurrence but remain at risk of regional recurrence. Oral tongue avoidance during adjuvant radiation therapy is an attractive potential treatment strategy to mitigate treatment toxicity. We sought to quantify the dosimetric advantages of this approach and hypothesized that intensity-modulated proton therapy (IMPT) may further reduce organs at risk doses compared with intensity-modulated radiation therapy (IMRT). Materials and Methods: Five patients with oral tongue cancer treated with postoperative radiation therapy from August 2020 to September 2021 were retrospectively reviewed. Novel clinical target volume contours, excluding the oral tongue, were generated while maintaining coverage of bilateral at-risk lymph nodes. Comparison IMRT (X) and IMPT (PBT) plans were generated using standard treatment volumes (control) and avoidance volumes (study) (n = 4 plans/patient). Dosimetric variables for organs at risk were compared using the paired t test. Results: The prescribed dose was 60 Gy in 30 fractions. D95% clinical target volume coverage was similar between X and PBT plans for both control and study clinical target volumes. Comparing control with study plans, both X (58.9 Gy vs 38.3 Gy, P = .007) and PBT (60.2 Gy vs 26.1 Gy, P < .001) decreased the oral cavity dosemean. The pharyngeal constrictor dosemean was also reduced (P < .003). There was no difference between control and study plans for larynx (P = .19), parotid (P = .11), or mandible dose (P = .59). For study plans, PBT significantly reduced oral cavity dosemean (38.3 Gy vs 26.1 Gy, P = .007) and parotid dosemean (23.3 Gy vs 19.3 Gy, P = .03) compared with X. For control plans, there was no difference in oral cavity dosemean using PBT compared with X, but PBT did improve the parotid dosemean (26.6 Gy vs 19.7 Gy, P = .02). Conclusion: This study quantifies the feasibility and dosimetric advantages of oral tongue avoidance while still treating the at-risk lymph nodes for oral tongue cancer. The dosimetric difference between PBT and X was most prominent with an oral tongue-avoidance strategy.

Quality Metric to Assess Adequacy of Hydrogel Rectal Spacer Placement for Prostate Radiation Therapy and Association of Metric Score With Rectal Toxicity Outcomes.

Purpose: Although hydrogel spacer placement (HSP) minimizes rectal dose during prostate cancer radiation therapy, its potential benefit for modulating rectal toxicity could depend on the achieved prostate-rectal separation. We therefore developed a quality metric associated with rectal dose reduction and late rectal toxicity among patients treated with prostate stereotactic body radiation therapy (SBRT). Methods and Materials: A quality metric consisting of prostate-rectal interspace measurements from axial T2-weighted magnetic resonance imaging simulation images was applied to 42 men enrolled in a multi-institutional phase 2 study using HSP with prostate SBRT (45 Gy in 5 fractions). A score of 0, 1, or 2 was assigned to a prostate-rectal interspace measurement of <0.3 cm, 0.3 to 0.9 cm, or ≥1 cm, respectively. An overall spacer quality score (SQS) was computed from individual scores at rectal midline and ±1 cm laterally, located at the prostate base, midgland, and apex. Associations of SQS with rectal dosimetry and late toxicity were evaluated. Results: The majority of the analyzed cohort had an SQS of 1 (n = 17; 41%) or 2 (n = 18; 43%). SQS was associated with maximum rectal point dose (rectal Dmax; P = .002), maximum dose to 1 cc of rectum (D1cc; P = .004), and volume of rectum receiving ≥100% of prescription dose (V45; P = .046) and ≥40 Gy (V40; P = .005). SQS was also associated with a higher incidence of (P = .01) and highest-graded late rectal toxicity (P = .01). Among the 20 men who developed late grade ≥1 rectal toxicity, 57%, 71%, and 22% had an SQS of 0, 1, and 2, respectively. Men with an SQS of 0 or 1 compared with 2 had 4.67-fold (95% CI, 0.72-30.11) or 8.40-fold (95% CI, 1.83-38.57) greater odds, respectively, of developing late rectal toxicity. Conclusions: We developed a reliable and informative metric for assessing HSP, which appears to be associated with rectal dosimetry and late rectal toxicity after prostate SBRT.

Post-operative PET/CT improves the detection of early recurrence of squamous cell carcinomas of the oral cavity.

BACKGROUND: We evaluate the impact of post-operative 18-fluorodeoxyglucose positron emission tomography with computed tomography (PET/CT) for radiation planning on the detection of early recurrence (ER) and treatment outcomes in oral squamous cell carcinoma (OSCC). METHODS: We retrospectively reviewed the records of patients treated with post-operative radiation between 2005 and 2019 for OSCC at our institution. Extracapsular extension and positive surgical margins were classified as high risk features; pT3-4, node positivity, lymphovascular invasion, perineural invasion, tumor thickness >5 mm, and close surgical margins were considered intermediate risk features. Patients with ER were identified. Inverse probability of treatment weighting (IPTW) was used to adjust for imbalances between baseline characteristics. RESULTS: 391 patients with OSCC were treated with post-operative radiation. 237 (60.6%) patients underwent post-operative PET/CT planning vs. 154 (39.4%) who were planned with CT only. Patients screened with post-operative PET/CT were more likely to be diagnosed with ER than those planned with CT only (16.5 vs. 3.3%, p < 0.0001). Among patients with ER, those with intermediate features were more likely than those high risk features to undergo major treatment intensification, including re-operation, the addition of chemotherapy, or intensification of radiation by ≥ 10 Gy (91% vs. 9%, p < 0.0001). Post-operative PET/CT was associated with improved disease-free and overall survival for patients with intermediate risk features (IPTW log-rank p = 0.026 and p = 0.047, respectively) but not high risk features (IPTW log-rank p = 0.44 and p = 0.96). CONCLUSIONS: Use of post-operative PET/CT is associated with increased detection of early recurrence. Among patients with intermediate risk features, this may translate to improved disease-free survival.

Evaluation of Proton Therapy Reirradiation for Patients With Recurrent Head and Neck Squamous Cell Carcinoma.

Importance: Use of proton therapy reirradiation (PT-ReRT) for head and neck cancer is increasing; however, reports are heterogenous and outcomes can be difficult to interpret. Objective: To evaluate outcomes and toxic effects following PT-ReRT in a uniform and consecutive cohort of patients with head and neck squamous cell carcinoma. Design, Setting, and Participants: This retrospective cohort study included patients with recurrent primary head and neck squamous cell carcinoma who were treated with PT-ReRT from January 1, 2013, to December 31, 2020, at a single institution. Patient, clinical, and treatment characteristics were obtained, and multidisciplinary review was performed to record and grade early and late toxic effects. Exposures: Proton therapy reirradiation. Main Outcomes and Measures: Follow-up was defined from the start of PT-ReRT. The Kaplan-Meier method was used for outcomes of interest, including local control (LC), locoregional control, distant metastatic control, progression-free survival, and overall survival (OS). Cox proportional hazards regression modeling was used to assess associations of covariates with OS. Results: A total of 242 patients (median [range] age, 63 [21-96] years; 183 [75.6%] male) were included. Of these patients, 231 (95.9%) had a Karnofsky performance status score of 70 or higher, and 145 (59.9%) had at least a 10-pack-year smoking history. Median (range) follow-up was 12.0 (5.8-26.0) months for all patients and 24.5 (13.8-37.8) months for living patients. A total of 206 patients (85.1%) had recurrent disease vs second primary or residual disease. The median (range) interval between radiation courses was 22 (1-669) months. Median PT-ReRT dose was 70 cobalt gray equivalents (CGE) for the fractionated cohort and 44.4 CGE for the quad shot cohort. For the fractionated cohort, the 1-year LC was 71.8% (95% CI, 62.8%-79.0%) and the 1-year OS was 66.6% (95% CI, 58.1%-73.8%). For the quad shot cohort, the 1-year LC was 61.6% (95% CI, 46.4%-73.6%) and the 1-year OS was 28.5% (95% CI, 19.4%-38.3%). Higher Karnofsky performance status scores (hazard ratio [HR], 0.50; 95% CI, 0.25-0.99; P = .046) and receipt of salvage surgery prior to PT-ReRT (HR, 0.57; 95% CI, 0.39-0.84; P = .005) were associated with improved OS, whereas receipt of quad shot (HR, 1.97; 95% CI, 1.36-2.86; P < .001) was associated with worse OS. There were a total of 73 grade 3 and 6 grade 4 early toxic effects. There were 79 potential grade 3, 4 grade 4, and 5 grade 5 late toxic effects. Conclusions and Relevance: The findings of this cohort study suggest that, compared with previous reports with photon-based reirradiation, patients are living longer with aggressive PT-ReRT; however, surviving patients remain at risk of early and late complications.

Intrarater and interrater reliability of the first metatarsophalangeal joint dorsiflexion resistance test.

BACKGROUND: The first metatarsophalangeal joint plays a fundamental role during the gait cycle. The Hubscher manoeuvre, which consists of passively dorsiflexing the first metatarsophalangeal joint of an individual in relaxed stance and observing the raising of the medial longitudinal arch, is a clinical test thought to examine the function of the first metatarsophalangeal joint. However, the hallux dorsiflexion achieved during this test is not related to hallux dorsiflexion during gait. On the other hand, unlike kinematic tests, results from kinetic tests have been shown to be strongly correlated with dynamic joint biomechanics. Thus, given the need for valid and reliable tests to evaluate the function of the first metatarsophalangeal joint, this study aimed to assess the reliability of a new kinetic test, namely, the first metatarsophalangeal joint dorsiflexion resistance test. METHOD: Thirty young adults completed two data collection sessions 1 week apart, during which the first metatarsophalangeal joint dorsiflexion resistance test was performed. Intrarater and interrater reliability were assessed using intraclass correlation coefficients (ICC), minimal detectable difference (MDD), standard error of the mean (SEM) and limits of agreements (LoA). RESULTS: For the intrarater reliability, the ICC was 0.77 (p < 0.001), the SEM was 6.5 N, the MDD was 18.1 N and the LoA were -7.9 to 26.9 N. For the interrater reliability, the ICC was 0.86 (p < 0.001), the SEM was 6.9 N, the MDD was 19.0 N and the LoA were -6.4 to 21.8 N. CONCLUSION: The results of this study demonstrate good intra and interrater reliability of the first metatarsophalangeal joint dorsiflexion resistance test, which provides evidence to support its use in clinical and research contexts. Further work is required to establish the test results' relationship with joint kinetics during gait and to provide normative values in individuals with and without musculoskeletal disorders as well as among different age groups and genders to optimise its utilization in clinical and research settings.

Comprehensive review of the use of hydrogel spacers prior to radiation therapy for prostate cancer.

OBJECTIVES: To provide a comprehensive narrative review of the published data on the impact of hydrogel spacers on rectal dosimetry and toxicity and to outline the practicalities of inserting hydrogel spacers. RESULTS: A growing body of evidence suggests that the administration of hydrogel spacers is safe and is associated with limited peri-operative morbidity. The impact on rectal dosimetry has been clearly established and use of hydrogel spacers is associated with reduced rectal morbidity. These results have been corroborated by several Phase II and III clinical trials and subsequent meta-analysis. There are several areas for future research, including the role of hydrogel spacers in prostate stereotactic beam radiotherapy and post-radiotherapy local recurrence. CONCLUSIONS: Hydrogel spacers provide a low-morbidity method to potential reduce rectal toxicity after radiation therapy in men with prostate cancer. Data outlining sexual function and oncological outcomes are limited to date. Future studies, currently being conducted, may provide further clarification of the role of hydrogel spacers in prostate cancer management.

Local Failure after Prostate SBRT Predominantly Occurs in the PI-RADS 4 or 5 Dominant Intraprostatic Lesion.

BACKGROUND: A positive post-treatment prostate biopsy following definitive radiotherapy carries significant prognostic implications. OBJECTIVE: To determine whether local recurrences after prostate stereotactic body radiation therapy (SBRT) are associated with the presence of and occur more commonly within the region of a PI-RADS 4 or 5 dominant intra-prostatic lesion (DIL) identified on pre-treatment multi-parametric magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: 247 patients with localized prostate cancer treated with SBRT at our institution from 2009-2018 underwent post-treatment biopsies (median time to biopsy: 2.2 years) to evaluate local control. INTERVENTIONS: Prostate SBRT (median 40 Gy in 5 fractions). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: MRIs were read by a single diagnostic radiologist blinded to other patient characteristics and treatment outcomes. The DIL presence, size, location, and extent were then analyzed to determine associations with the post-treatment biopsy outcomes. RESULTS AND LIMITATIONS: Among patients who underwent post-treatment biopsies, 39/247 (15.8%) were positive for Gleason-gradable prostate adenocarcinoma, of which 35/39 (90%) had a DIL initially present and 29/39 (74.4%) had a positive biopsy within the DIL. Factors independently associated with post-treatment biopsy outcomes included the presence of a DIL (OR 6.95; p = 0.001), radiographic T3 disease (OR 5.23, p < 0.001), SBRT dose ≥40 Gy (OR 0.26, p = 0.003), and use of androgen deprivation therapy (ADT; OR 0.28, p = 0.027). Among patients with a DIL (N = 149), the only factors associated with post-treatment biopsy outcomes included ≥50% percent cores positive (OR 2.4, p = 0.037), radiographic T3 disease (OR 4.04, p = 0.001), SBRT dose ≥40 Gy (OR 0.22, p < 0.001), and use of ADT (OR 0.21, p = 0.014). CONCLUSIONS: Our results suggest that men with PI-RADS 4 or 5 DILs have a higher risk of local recurrence after prostate SBRT and that most recurrences are located within the DIL. PATIENT SUMMARY: We found the presence of a dominant tumor on pre-treatment MRI was strongly associated with residual cancer within the prostate after SBRT and that most recurrences were within the dominant tumor.