Evaluating machine learning enhanced intelligent-optimization-engine (IOE) performance for ethos head-and-neck (HN) plan generation.

PURPOSE: Varian Ethos utilizes novel intelligent-optimization-engine (IOE) designed to automate the planning. However, this introduced a black box approach to plan optimization and challenge for planners to improve plan quality. This study aims to evaluate machine-learning-guided initial reference plan generation approaches for head & neck (H&N) adaptive radiotherapy (ART). METHODS: Twenty previously treated patients treated on C-arm/Ring-mounted were retroactively re-planned in the Ethos planning system using a fixed 18-beam intensity-modulated radiotherapy (IMRT) template. Clinical goals for IOE input were generated using (1) in-house deep-learning 3D-dose predictor (AI-Guided) (2) commercial knowledge-based planning (KBP) model with universal RTOG-based population criteria (KBP-RTOG) and (3) an RTOG-based constraint template only (RTOG) for in-depth analysis of IOE sensitivity. Similar training data was utilized for both models. Plans were optimized until their respective criteria were achieved or DVH-estimation band was satisfied. Plans were normalized such that the highest PTV dose level received 95% coverage. Target coverage, high-impact organs-at-risk (OAR) and plan deliverability was assessed in comparison to clinical (benchmark) plans. Statistical significance was evaluated using a paired two-tailed student t-test. RESULTS: AI-guided plans were superior to both KBP-RTOG and RTOG-only plans with respect to clinical benchmark cases. Overall, OAR doses were comparable or improved with AI-guided plans versus benchmark, while they increased with KBP-RTOG and RTOG plans. However, all plans generally satisfied the RTOG criteria. Heterogeneity Index (HI) was on average <1.07 for all plans. Average modulation factor was 12.2 ± 1.9 (p = n.s), 13.1 ± 1.4 (p = <0.001), 11.5 ± 1.3 (p = n.s.) and 12.2 ± 1.9 for KBP-RTOG, AI-Guided, RTOG and benchmark plans, respectively. CONCLUSION: AI-guided plans were the highest quality. Both KBP-enabled and RTOG-only plans are feasible approaches as clinics adopt ART workflows. Similar to constrained optimization, the IOE is sensitive to clinical input goals and we recommend comparable input to an institution's planning directive dosimetric criteria.

Long-term opioid use in patients treated with head and neck intensity-modulated radiotherapy.

PURPOSE: Acute and chronic pain during and after radiotherapy is an important driver of poor quality of life. We aimed to identify risk factors associated with increased chronic opioid use in head and neck squamous cell cancer survivors. METHODS: We performed a retrospective cohort analysis on head and neck squamous cell cancer patients treated with definitive or adjuvant intensity-modulated radiotherapy. We tracked their oncologic opioid prescription profile from initial presentation to the last follow-up date. We determined the incidences of 1- and 2-year opioid use and performed multivariate logistic regression for both outcomes. RESULTS: Our analytic cohort consisted of 403 head and neck squamous cell cancer survivors. The numbers of patients requiring opioids at 3 months, 6 months, and 1 year after treatment were 316 (78%), 203 (50%), and 102 (25%), respectively. On multivariate logistic regression, positive smoking history (95% CI 1.86 [1.03, 3.43], p = 0.04), unemployment (95% CI 2.33 [1.16, 4.67], p = 0.02), prior psychiatric illness (95% CI 2.15 [1.05, 4.40], p = 0.03), and opiate use before radiotherapy (95% CI 2.75 [1.49, 5.20], p = 0.01) were independently associated with significantly greater odds of opioid use at 1 year. CONCLUSIONS: Our institutional analysis has shown that a substantial amount of head and neck cancer survivors are chronically dependent on opioids following radiotherapy. We have identified a cohort at highest risk for long-term use, for whom early interventions should be targeted.

NCCN Guidelines® Insights: Older Adult Oncology, Version 1.2021.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Phase I/II trial of nano-camptothecin CRLX101 with capecitabine and radiotherapy as neoadjuvant treatment for locally advanced rectal cancer.

CRLX101 is a nanoparticle-drug conjugate with a camptothecin payload. We assessed the toxicity and pathologic complete response (pCR) rate of CRLX101 with standard neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. A single-arm study was conducted with a 3 + 3 dose escalation phase Ib followed by phase II at the maximum tolerated dose (MTD). Thirty-two patients were enrolled with 29 (91%) patients having T3/4 and 26 (81%) N1/2 disease. In phase Ib, no patient experienced a dose limiting toxicity (DLT) with every other week dosing, while 1/9 patients experienced a DLT with weekly dosing. The weekly MTD was identified as 15 mg/m2. The most common grade 3-4 toxicity was lymphopenia, with only 1 grade 4 event. pCR was achieved in 6/32 (19%) patients overall and 2/6 (33%) patients at the weekly MTD. CRLX101 at 15 mg/m2 weekly with neoadjuvant CRT is a feasible combination strategy with an excellent toxicity profile. Clinicaltrials.gov registration NCT02010567.

Targeted radiosensitization with PARP1 inhibition: optimization of therapy and identification of biomarkers of response in breast cancer.

Sustained locoregional control of breast cancer is a significant issue for certain patients. Inhibition of PARP1 is a promising strategy for radiosensitization (RS). We sought to optimize therapy with PARP1 inhibition and radiation (RT) by establishing the most effective treatment schedule, degree of PARP1-mediated RS, and identify early biomarkers predictive of efficacy in breast cancer models. Using clonogenic survival assays, we assessed intrinsic radiosensitivity and RS induced by PARP1 inhibition in breast cancer cell lines. Potential biomarkers of response were evaluated using western blotting, flow cytometry, and immunofluorescence with validation in vivo using tumor xenograft experiments. Across a panel of BC and normal breast epithelial cell lines, the PARP1 inhibitor ABT-888 preferentially radiosensitizes breast cancer (vs. normal) cells with enhancement ratios (EnhR) up to 2.3 independent of intrinsic BC subtype or BRCA mutational status. Concurrent and adjuvant therapy resulted in the highest EnhR of all schedules tested. The degree of RS did not correlate with pretreatment markers of PARP1 activity, DNA damage/repair, or cell cycle distribution. Increases in PARP1 activity 24 h after RT were associated with sensitivity after combination treatment. Findings were confirmed in breast cancer xenograft models. Our study demonstrates that PARP1 inhibition improves the therapeutic index of RT independent of BC subtype or BRCA1 mutational status and that PARP1 activity may serve as a clinically relevant biomarker of response. These studies have led to a clinical trial (TBCRC024) incorporating intratreatment biomarker analyses of PARP1 inhibitors and RT in breast cancer patients.

In Silico Analysis of Adjuvant Head and Neck Online Adaptive Radiation Therapy.

Purpose: Recently developed online adaptive radiation therapy (OnART) systems enable frequent treatment plan adaptation, but data supporting a dosimetric benefit in postoperative head and neck radiation therapy (RT) are sparse. We performed an in silico dosimetric study to assess the potential benefits of a single versus weekly OnART in the treatment of patients with head and neck squamous cell carcinoma in the adjuvant setting. Methods and Materials: Twelve patients receiving conventionally fractionated RT over 6 weeks and 12 patients receiving hypofractionated RT over 3 weeks on a clinical trial were analyzed. The OnART emulator was used to virtually adapt either once midtreatment or weekly based on the patient's routinely performed cone beam computed tomography. The planning target volume (PTV) coverage, dose heterogeneity, and cumulative dose to the organs at risk for these 2 adaptive approaches were compared with the nonadapted plan. Results: In total, 13, 8, and 3 patients had oral cavity, oropharynx, and larynx primaries, respectively. In the conventionally fractionated RT cohort, weekly OnART led to a significant improvement in PTV V100% coverage (6.2%), hot spot (-1.2 Gy), and maximum cord dose (-3.1 Gy), whereas the mean ipsilateral parotid dose increased modestly (1.8 Gy) versus the nonadapted plan. When adapting once midtreatment, PTV coverage improved with a smaller magnitude (0.2%-2.5%), whereas dose increased to the ipsilateral parotid (1.0-1.1 Gy) and mandible (0.2-0.7 Gy). For the hypofractionated RT cohort, similar benefit was observed with weekly OnART, including significant improvement in PTV coverage, hot spot, and maximum cord dose, whereas no consistent dosimetric advantage was seen when adapting once midtreatment. Conclusions: For head and neck squamous cell carcinoma adjuvant RT, there was a limited benefit of single OnART, but weekly adaptations meaningfully improved the dosimetric criteria, predominantly PTV coverage and dose heterogeneity. A prospective study is ongoing to determine the clinical benefit of OnART in this setting.

In silico evaluation and feasibility of near margin-less head and neck daily adaptive radiotherapy.

OBJECTIVE: We explore the potential dosimetric benefits of reducing treatment volumes through daily adaptive radiation therapy for head and neck cancer (HNC) patients using the Ethos system/Intelligent Optimizer Engine (IOE). We hypothesize reducing treatment volumes afforded by daily adaption will significantly reduce the dose to adjacent organs at risk. We also explore the capability of the Ethos IOE to accommodate this highly conformal approach in HNC radiation therapy. METHODS: Ten HNC patients from a phase II trial were chosen, and their cone-beam CT (CBCT) scans were uploaded to the adaptive RT (ART) emulator. A new initial reference plan was generated using both a 1 mm and 5 mm planning target volume (PTV) expansion. Daily adaptive ART plans (1 mm) were simulated from the clinical CBCT taken every fifth fraction. Additionally, using physician-modified ART contours the larger 5 mm plan was recalculated on this recontoured on daily anatomy. Changes in target and OAR contours were measured using Dice coefficients as a surrogate of clinician effort. PTV coverage and organ-at-risk (OAR) doses were statistically compared, and the robustness of each ART plan was evaluated at fractions 5 and 35 to observe if OAR doses were within 3 Gy of pre-plan. RESULTS: This study involved six patients with oropharynx and four with larynx cancer, totaling 70 adaptive fractions. The primary and nodal gross tumor volumes (GTV) required the most adjustments, with median Dice scores of 0.88 (range: 0.80-0.93) and 0.83 (range: 0.66-0.91), respectively. For the 5th and 35th fraction plans, 80 % of structures met robustness criteria (quartile 1-3: 67-100 % and 70-90 %). Adaptive planning improved median PTV V100% coverage for doses of 70 Gy (96 % vs. 95.6 %), 66.5 Gy (98.5 % vs. 76.5 %), and 63 Gy (98.9 % vs. 74.9 %) (p < 0.03). Implementing ART with total volume reduction yielded median dose reductions of 7-12 Gy to key organs-at-risk (OARs) like submandibular glands, parotids, oral cavity, and constrictors (p < 0.05). CONCLUSIONS: The IOE enables feasible daily ART treatments with reduced margins while enhancing target coverage and reducing OAR doses for HNC patients. A phase II trial recently finished accrual and forthcoming analysis will determine if these dosimetric improvements correlate with improved patient-reported outcomes.

Artificial intelligence guided physician directive improves head and neck planning quality and practice Uniformity: A prospective study.

•AI dose predictor was fully integrated with treatment planning system and used as a physicain decision support tool to improve uniformity of practice.•Model was trained based on our standard of practice, but implemented at the time of expansion with 3 new physicians join the practice.•Phase 1 retrospective evaluation demonstrated the non-uniform practice among 3 MDs and only 52.9% frequency planner can achieve physicians' directives.•Significant improvement in practice uniformity of practice was observed after utilizing AI as DST and 80.4% frequency clinical plan can achieve AI-guided physician directives.

Early Experience of Online Adaptive Radiation Therapy for Definitive Radiation of Patients With Head and Neck Cancer.

Purpose: The advent of cone beam computed tomography-based online adaptive radiation therapy (oART) has dramatically reduced the barriers of adaptation. We present the first prospective oART experience data in radiation of head and neck cancers (HNC). Methods and Materials: Patients with HNC receiving definitive standard fractionation (chemo)radiation who underwent at least 1 oART session were enrolled in a prospective registry study. The frequency of adaptations was at the discretion of the treating physician. Physicians were given the option of delivering 1 of 2 plans during adaptation: the original radiation plan transposed onto the cone beam computed tomography with adapted contours (scheduled), and a new adapted plan generated from the updated contours (adapted). A paired t test was used to compare the mean doses between scheduled and adapted plans. Results: Twenty-one patients (15 oropharynx, 4 larynx/hypopharynx, 2 other) underwent 43 adaptation sessions (median, 2). The median ART process time was 23 minutes, median physician time at the console was 27 minutes, and median patient time in the vault was 43.5 minutes. The adapted plan was chosen 93% of the time. The mean volume in each planned target volume (PTV) receiving 100% of the prescription dose for the scheduled versus adapted plan for high-risk PTVs was 87.8% versus 95% (P < .01), intermediate-risk PTVs was 87.3% versus 97.9% (P < .01), and low-risk PTVs was 94% versus 97.8% (P < .01), respectively. The mean hotspot was also lower with adaptation: 108.8% versus 106.4% (P < .01). All but 1 organ at risk (11/12) saw a decrease in their dose with the adapted plans, with the mean ipsilateral parotid (P = .013), mean larynx (P < .01), maximum point spinal cord (P < .01), and maximum point brain stem (P = .035) reaching statistical significance. Conclusions: Online ART is feasible for HNC, with significant improvement in target coverage and homogeneity and a modest decrease in doses to several organs at risk.

Efficacy and Quality-of-Life Following Involved Nodal Radiotherapy for Head and Neck Squamous Cell Carcinoma: The INRT-AIR Phase II Clinical Trial.

PURPOSE: Elective neck irradiation (ENI) has long been considered mandatory when treating head and neck squamous cell carcinoma (HNSCC) with definitive radiotherapy, but it is associated with significant dose to normal organs-at-risk (OAR). In this prospective phase II study, we investigated the efficacy and tolerability of eliminating ENI and strictly treating involved and suspicious lymph nodes (LN) with intensity-modulated radiotherapy. PATIENTS AND METHODS: Patients with newly diagnosed HNSCC of the oropharynx, larynx, and hypopharynx were eligible for enrollment. Each LN was characterized as involved or suspicious based on radiologic criteria and an in-house artificial intelligence (AI)-based classification model. Gross disease received 70 Gray (Gy) in 35 fractions and suspicious LNs were treated with 66.5 Gy, without ENI. The primary endpoint was solitary elective volume recurrence, with secondary endpoints including patterns-of-failure and patient-reported outcomes. RESULTS: Sixty-seven patients were enrolled, with 18 larynx/hypopharynx and 49 oropharynx cancer. With a median follow-up of 33.4 months, the 2-year risk of solitary elective nodal recurrence was 0%. Gastrostomy tubes were placed in 14 (21%), with median removal after 2.9 months for disease-free patients; no disease-free patient is chronically dependent. Grade I/II dermatitis was seen in 90%/10%. There was no significant decline in composite MD Anderson Dysphagia Index scores after treatment, with means of 89.1 and 92.6 at 12 and 24 months, respectively. CONCLUSIONS: These results suggest that eliminating ENI is oncologically sound for HNSCC, with highly favorable quality-of-life outcomes. Additional prospective studies are needed to support this promising paradigm before implementation in any nontrial setting.

Oligometastasis in Head and Neck Squamous Cell Carcinoma.

Up to 40% of patients who present with, or later develop, metastatic disease from head and neck squamous cell carcinoma have oligometastatic disease, defined as 5 or fewer sites of metastasis. Patients with limited number of metastases clearly have improved overall survival compared with those with more disseminated metastases, but the risk of, and factors associated with, true oligometastatic state in head and neck cancer are not yet known. Current standard of care for patients with metastatic disease is single agent or combination systemic therapy, but the data are accumulating on the role of both metastasis-directed local ablative therapy and locoregional radiation therapy to improve outcomes. Although surgical resection has been the treatment of choice to address oligometastasis historically, stereotactic ablative radiotherapy has become a viable and less invasive alternative option with encouraging retrospective data in head and neck cancers. Biomarkers to help identify the oligometastatic state and prospective studies to better elucidate the role of local therapies are urgently needed.

Survival and disease progression following solitary locoregional recurrence after head and neck radiotherapy.

PURPOSE: The management of solitary locoregional recurrence (sLRR) of head and neck squamous cell carcinoma (HNSCC) previously treated with radiotherapy (RT) is challenging. We aimed to identify characteristics associated with improved outcome. METHODS: We identified patients treated with non-sinus, mucosal HNSCC who initially received IMRT. We characterized overall survival (OS) and locoregional control (LRC). Multivariable analysis (MVA) on survival and patterns-of-failure were performed using Cox and Fine-Gray competing risks analysis. RESULTS: We identified 90 patients with available follow-up. In total, 67 (74%) patients received curative-intent salvage, while 23 (26%) received palliative care. On MVA, significantly improved OS and LRC were associated with lower initial N-classification and use of salvage total laryngectomy (TL) or neck dissection (ND). CONCLUSION: A nontrivial number of patients with sLRR cannot undergo salvage. Among patients treated with curative intent, TL or ND were clearly associated with improved OS and LRC.

Registration-guided deep learning image segmentation for cone beam CT-based online adaptive radiotherapy.

PURPOSE: Adaptive radiotherapy (ART), especially online ART, effectively accounts for positioning errors and anatomical changes. One key component of online ART process is accurately and efficiently delineating organs at risk (OARs) and targets on online images, such as cone beam computed tomography (CBCT). Direct application of deep learning (DL)-based segmentation to CBCT images suffered from issues such as low image quality and limited available contour labels for training. To overcome these obstacles to online CBCT segmentation, we propose a registration-guided DL (RgDL) segmentation framework that integrates image registration algorithms and DL segmentation models. METHODS: The RgDL framework is composed of two components: image registration and RgDL segmentation. The image registration algorithm transforms/deforms planning contours that were subsequently used as guidance by the DL model to obtain accurate final segmentations. We had two implementations of the proposed framework-Rig-RgDL (Rig for rigid body) and Def-RgDL (Def for deformable)-with rigid body (RB) registration or deformable image registration (DIR) as the registration algorithm, respectively, and U-Net as the DL model architecture. The two implementations of RgDL framework were trained and evaluated on seven OARs in an institutional clinical head-and-neck dataset. RESULTS: Compared to the baseline approaches using the registration or the DL alone, RgDLs achieved more accurate segmentation, as measured by higher mean Dice similarity coefficients (DSCs) and other distance-based metrics. Rig-RgDL achieved a DSC of 84.5% on seven OARs on average, higher than RB or DL alone by 4.5% and 4.7%. The average DSC of Def-RgDL was 86.5%, higher than DIR or DL alone by 2.4% and 6.7%. The inference time required by the DL model component to generate final segmentations of seven OARs was less than 1 s in RgDL. By examining the contours from RgDLs and DL case by case, we found that RgDL was less susceptible to image artifacts. We also studied how the performances of RgDL and DL vary with the size of the training dataset. The DSC of DL dropped by 12.1% as the number of training data decreased from 22 to 5, whereas RgDL only dropped by 3.4%. CONCLUSION: By incorporating the patient-specific registration guidance to a population-based DL segmentation model, RgDL framework overcame the obstacles associated with online CBCT segmentation, including low image quality and insufficient training data, and achieved better segmentation accuracy than baseline methods. The resulting segmentation accuracy and efficiency show promise for applying this RgDL framework for online ART.

Receipt of Guideline-Recommended Surveillance in a Population-Based Cohort of Prostate Cancer Patients Undergoing Active Surveillance.

PURPOSE: Prospective clinical trials have demonstrated the safety and efficacy of active surveillance for men with localized prostate cancer but also suggested that inadequate surveillance may risk missing an opportunity for cure. METHODS AND MATERIALS: We used data from a population-based cohort of active-surveillance patients to examine the rigor of surveillance monitoring in the general population. RESULTS: Among 1419 patients enrolled from 2011 to 2013 throughout the state of North Carolina in collaboration with the state cancer registry and followed prospectively, 346 pursued active surveillance. Only 13% received all guideline-recommended surveillance testing (including prostate-specific antigen, digital rectal examination, and prostate biopsy) within the first 2 years. Furthermore, adherence was <20% in all patient subgroups. CONCLUSIONS: These findings suggest that "active surveillance" as implemented in the general population may not represent the rigorous monitoring regimens used in the studies that demonstrated the safety of this management approach. More real-world studies on active surveillance are needed.

NTCP modeling and dose-volume correlations for acute xerostomia and dry eye after whole brain radiation.

BACKGROUND: Whole brain radiation (WBRT) may lead to acute xerostomia and dry eye from incidental parotid and lacrimal exposure, respectively. We performed a prospective observational study to assess the incidence/severity of this toxicity. We herein perform a secondary analysis relating parotid and lacrimal dosimetric parameters to normal tissue complication probability (NTCP) rates and associated models. METHODS: Patients received WBRT to 25-40 Gy in 10-20 fractions using 3D-conformal radiation therapy without prospective delineation of the parotids or lacrimals. Patients completed questionnaires at baseline and 1 month post-WBRT. Xerostomia was assessed using the University of Michigan xerostomia score (scored 0-100, toxicity defined as ≥ 20 pt increase) and xerostomia bother score (scored from 0 to 3, toxicity defined as ≥ 2 pt increase). Dry eye was assessed using the Subjective Evaluation of Symptom of Dryness (SESoD, scored from 0 to 4, toxicity defined as ≥ 2 pt increase). The clinical data were fitted by the Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) NTCP models. RESULTS: Of 55 evaluable patients, 19 (35%) had ≥ 20 point increase in xerostomia score, 11 (20%) had ≥ 2 point increase in xerostomia bother score, and 13 (24%) had ≥ 2 point increase in SESoD score. For xerostomia, parotid V10Gy-V20Gy correlated best with toxicity, with AUC 0.68 for xerostomia score and 0.69-0.71 for bother score. The values for the D50, m and n parameters of the LKB model were 22.3 Gy, 0.84 and 1.0 for xerostomia score and 28.4 Gy, 0.55 and 1.0 for bother score, respectively. The corresponding values for the D50, γ and s parameters of the RS model were 23.5 Gy, 0.28 and 0.0001 for xerostomia score and 32.0 Gy, 0.45 and 0.0001 for bother score, respectively. For dry eye, lacrimal V10Gy-V15Gy were found to correlate best with toxicity, with AUC values from 0.67 to 0.68. The parameter values of the LKB model were 53.5 Gy, 0.74 and 1.0, whereas of the RS model were 54.0 Gy, 0.37 and 0.0001, respectively. CONCLUSIONS: Xerostomia was most associated with parotid V10Gy-V20Gy, and dry eye with lacrimal V10Gy-V15Gy. NTCP models were successfully created for both toxicities and may help clinicians refine dosimetric goals and assess levels of risk in patients receiving palliative WBRT.

Prognostic impact of matted lymphadenopathy in patients with oropharyngeal squamous cell carcinoma treated with definitive chemoradiotherapy.

OBJECTIVE: To determine whether cervical matted lymphadenopathy (ML) is associated with outcomes in patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive chemoradiotherapy (CRT). MATERIALS AND METHODS: OPSCC patients treated at our institution with CRT were included (n = 417). ML was defined by three adjacent nodes without an intervening fat plane. Patients were stratified into favorable OPSCC (p16 + with ≤ 10 pack-years smoking history) or unfavorable OPSCC (p16- and/or > 10 pack years). Primary outcomes were overall survival (OS) and progression-free survival (PFS) and the cumulative incidences of regional recurrence (RR) and distant metastasis (DM). RESULTS: The median follow-up time for the surviving cohort was 49.9 months. In favorable OPSCC (n = 220), there were no significant associations between ML and any outcome. In unfavorable OPSCC (n = 197), ML had a significant negative impact on OS and PFS, with 3-year OS for patients without and with matted nodes at 74% and 56% (HR, 1.61, 95% CI 1.01-2.58). On multivariable Cox regression, patients with ML experienced significantly worsened OS (HR 1.65, 95% CI 1.03-2.65) and PFS (HR 1.94, 95% CI 1.28-2.93). The cumulative incidence of DM was also higher with ML (31% vs. 9%, adjusted HR 3.3, 95% CI 1.71-6.48). CONCLUSION: ML carries no prognostic importance in patients with favorable OPSCC. However, ML portends significantly worse outcomes in individuals with HPV-negative disease or a significant smoking history. Thus, ML may help risk-stratify this latter population for treatment intensification, but does not seem to be a contraindication for treatment de-escalation in the former.

PIK3CA Mutation in HPV-Associated OPSCC Patients Receiving Deintensified Chemoradiation.

PIK3CA is the most frequently mutated gene in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Seventy-seven patients with HPV-associated OPSCC were enrolled on two phase II clinical trials of deintensified CRT (60 Gy intensity-modulated radiotherapy with concurrent weekly cisplatin). Targeted next-generation sequencing was performed. Of the 77 patients, nine had disease recurrence (two regional, four distant, three regional and distant). Thirty-four patients had mutation(s) identified; 16 had PIK3CA mutations. Patients with wild-type-PIK3CA had statistically significantly higher 3-year disease-free survival than PIK3CA-mutant patients (93.4%, 95% confidence interval [CI] = 85.0% to 99.9% vs 68.8%, 95% CI = 26.7% to 89.8%; P = .004). On multivariate analysis, PIK3CA mutation was the only variable statistically significantly associated with disease recurrence (hazard ratio = 5.71, 95% CI = 1.53 to 21.3; P = .01). PIK3CA mutation is associated with worse disease-free survival in a prospective cohort of newly diagnosed HPV-associated OPSCC patients treated with deintensified CRT.

Clinician-observed and patient-reported toxicities and their association with poor tolerance to therapy in older patients with head and neck or lung cancer treated with curative radiotherapy.

OBJECTIVES: The agreement between clinician- and patient-reported toxicities and their association with poor tolerance to therapy were assessed in an older population receiving curative radiotherapy (RT). MATERIALS AND METHODS: Patients ≥ 65 years old with newly-diagnosed head and neck or lung cancer receiving curative RT ±â€¯chemotherapy were enrolled on a prospective, observational study. Agreement between clinician (CTCAEv4.02) and patient (PRO-CTCAE, EORTC QLQ-C30) report of toxicities were assessed at baseline, during treatment, and post-treatment. The association of clinician- and patient-reported symptoms with poor tolerance to therapy (defined as hospitalization, >3-day treatment delay, change in treatment regimen, or death) was assessed. RESULTS: Among 45 patients, median age was 71, 60% had head and neck cancer, and 47% received concurrent chemotherapy with RT. In comparing CTCAE vs PRO-CTCAE, there was good agreement at baseline except for fatigue, anorexia, and pain, where clinicians under-reported the severity. The discrepancy increased during treatment with clinicians reporting lower severity in ≥50% of matched pairs for 4/10 symptoms assessed. At follow-up, clinicians under-reported severity in ≥50% of pairs for 7/10 symptoms. CTCAE vs EORTC QLQ-C30 mirrored these findings. Patient-reported symptoms of nausea and dysphagia at 2 weeks and clinician-observed symptoms of nausea and dysphagia at 4 weeks were associated with poor tolerance to therapy. CONCLUSION: Clinicians under-report toxicities during and after curative RT in older patients with head and neck or lung cancer. Select toxicities reported by patients early in treatment and clinicians later in treatment were associated with poor tolerance to cancer therapy, providing valuable complementary information.

Patient-reported Quality of Life Following Stereotactic Body Radiotherapy and Conventionally Fractionated External Beam Radiotherapy Compared with Active Surveillance Among Men with Localized Prostate Cancer.

BACKGROUND: Evidence supporting the efficacy of stereotactic body radiotherapy (SBRT) for localized prostate cancer is accumulating, but comparative studies of patient-reported quality of life (QOL) following SBRT versus conventionally fractionated external beam radiotherapy (EBRT) or active surveillance (AS) are limited. OBJECTIVE: To compare QOL of patients pursuing SBRT and EBRT versus AS. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort of 680 men with newly diagnosed localized prostate cancer was prospectively enrolled from 2011 to 2013. INTERVENTION: SBRT, EBRT without androgen deprivation therapy, or AS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: QOL was prospectively assessed before treatment (baseline), and at 3, 12, and 24mo after treatment using the validated Prostate Cancer Symptom Indices, which contain four domains: sexual dysfunction, urinary obstruction/irritation, urinary incontinence, and bowel problems. Propensity weighting via logistic regression models was used to balance baseline characteristics, and the mean QOL scores of EBRT and SBRT patients were compared against AS patients as the control group. RESULTS AND LIMITATIONS: Compared with AS patients, EBRT patients had worse urinary obstructive/irritative symptoms and sexual dysfunction at 3mo, and worse bowel symptoms at 3 and 24mo. SBRT patients had similar scores as AS patients in all domains and across all time points; however, due to small sample size, worse sexual function and urinary incontinence in SBRT patients cannot be ruled out. Further research is needed to assess long-term outcomes. CONCLUSIONS: In a nonrandomized cohort of men with localized prostate cancer, SBRT appeared to result in favorable QOL results through 2yr of follow-up, but worse sexual function and urinary incontinence compared with AS cannot be ruled out completely. Larger studies with longer follow-up are needed to confirm these findings. PATIENT SUMMARY: Stereotactic body radiotherapy (SBRT) and active surveillance appear to have similar quality of life outcomes through 2yr, although worse sexual function and urinary incontinence from SBRT cannot be ruled out completely.

Shoulder symptoms and quality of life impact of limited neck dissection after de-intensified chemoradiotherapy: Secondary analysis of two prospective trials.

BACKGROUND: We investigated the quality of life (QOL) impact of post-radiation therapy (RT) superselective/selective neck dissection after de-intensified chemoradiation for human papillomavirus-associated oropharynx cancer. METHODS: A total of 147 patients received 60 Gy and weekly low-dose cisplatin on two phase 2 trials with planned post-RT neck dissection or surveillance positron emission tomography with neck dissection reserved for salvage. UW-QOL Shoulder Score, EORTC H&N-35, and EAT-10 were assessed. RESULTS: In all, 48 of 147 patients had post-RT neck dissection. At 2 years, 37% and 13% of patients receiving post-RT neck dissection had Shoulder Score ≥ 1 (any shoulder symptoms) and ≥ 2 (symptoms affecting work/hobbies), respectively, versus only 16% and 3% of patients not receiving post-RT neck dissection. Post-RT neck dissection was associated with Shoulder Score ≥ 1 (P = 0.005) and Shoulder Score ≥ 2 (P = 0.03) at 2 years, but not H&N-35 or EAT-10 scores. CONCLUSIONS: Post-RT superselective/selective neck dissection was associated with modest but persistent shoulder symptoms. These toxicities should be weighed against the probability of persistent disease when evaluating patients for post-RT neck dissection.