Quality of Life and Depression Symptoms After Therapy De-Escalation in HPV+ Oropharyngeal Squamous Cell Carcinoma: A Nonrandomized Controlled Trial.

Importance: Despite interest in therapy de-escalation for survivors of human papillomavirus-mediated oropharyngeal squamous cell carcinoma (HPV-positive OPSCC), the association of de-escalated therapy with patient-reported quality of life (QoL) outcomes and burden of depressive symptoms remains unclear. Objective: To identify associations between clinicopathologic and therapeutic variables with patient-reported QoL outcomes and depression symptom burden in patients with HPV-positive OPSCC, who were enrolled in a therapy de-escalation trial. Design, Setting, and Participants: In this nonrandomized controlled, open-label, curative-intent therapy de-escalation clinical trial in adults with stage I, II, and III HPV-positive OPSCC, patients were recruited from a high-volume head and neck oncology practice. Main Outcomes and Measures: The main outcomes of this study included quantitative, patient-reported QoL and depression symptoms per well-validated inventories. Patient-reported QoL was based on Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) scores (range, 0-148; lower score indicates inferior QoL). Patient-reported depression-related symptom burden was based on Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) scores (range, 0-27; a higher score indicates a higher burden of depression symptoms). Baseline clinicopathologic and treatment variables were paired with FACT-HN and QIDS-SR scores at baseline, 3, 6, 12, 24, and 36 months. Linear mixed-effect models with a random intercept were used for each participant and fixed effects for other measures. Regression coefficients are reported with 95% CIs. Results: A total of 95 patients were followed up for a median (IQR) of 2.2 (1.6-3.2) years. Of these, 93 patients (98%) were male with a mean (SD) age of 60.5 (8.2) years. Overall, 54 participants (57%) had a history of current or former smoking, 47 (50%) underwent curative-intent surgery (with or without adjuvant therapy), and 48 (50%) underwent primary radiotherapy (with or without chemotherapy). The median (IQR) radiotherapy dose was 60 (60-70) Gy. Five deaths and 2 recurrence events were observed (mean [SD] recurrence interval, 1.4 [1.5] years). A higher radiotherapy dose was the only modifiable factor associated with inferior patient-reported QoL (lower FACT-HN) (coefficient, -0.66 [95% CI, -1.09 to -0.23]) and greater burden of depression-related symptoms (higher QIDS-SR) (coefficient, 0.11 [95% CI, 0.04-0.19]). With the 70-Gy dose as reference, improvements in FACT-HN and QIDS-SR scores were identified when patients received 51 to 60 Gy (coefficient, 12.75 [95% CI, 4.58-20.92] and -2.17 [-3.49 to -0.85], respectively) and 50 Gy or lower (coefficient, 15.03 [4.36-25.69] and -2.80 [-4.55 to -1.04]). Conclusions and Relevance: In this nonrandomized controlled, open-label, curative-intent therapy de-escalation trial, a higher radiotherapy dose was associated with inferior patient-reported QoL and a greater burden of depression-related symptoms. This suggests opportunities for improved QoL outcomes and reduced depression symptom burden with a reduction in radiotherapy dose. Trial Registration: ClinicalTrials.gov Identifier: NCT04638465.

The Relationship between Animation Deformity and Patient-Reported Outcomes: Application of the BREAST-Q to a Quantitative Stratification of Animation Severity.

BACKGROUND: Animation deformity can occur following subpectoral breast reconstruction and is an oft-touted rationale for prepectoral reconstruction. Despite increasing recognition, there is a paucity of patient-reported outcome studies in women with animation deformity. METHODS: Women presenting after subpectoral implant-based breast reconstruction were evaluated for animation deformity. Video analysis and quantitative deformity assessment were performed in conjunction with BREAST-Q surveys. BREAST-Q data were compared to our quantitative animation grading scale to assess the relationship between animation severity and patient-reported outcomes. RESULTS: One hundred forty-one subpectoral breast reconstructions met inclusion criteria. Average scores were 67.8 ± 17.9 of 100 for satisfaction with breasts and 78.3 ± 14.1 of 100 for physical well-being. Animation deformity severity did not correlate with satisfaction with breasts (p = 0.44). Physical well-being, particularly pain-related questions, increased with increasing animation (p = 0.01); specifically, patients reported significantly less pulling, nagging, and aching in the breast (p = 0.01, p = 0.001, and p = 0.004, respectively). Patients with the least and most severe animation deformity had significantly higher numbers of revision procedures (0.89 and 1.03 procedures, respectively) compared with patients with intermediate deformity (0.49 procedures; p = 0.01 and p = 0.009, respectively). CONCLUSIONS: Although pectoralis release creates a more mobile-and more animating-reconstruction, this same release may lead to less pain because muscle is no longer contracting against a fixed space. This may lead to two distinct origins of subpectoral revision: (1) patients in pain (but low animation) and (2) patients with visibly distorted animation (but low pain). CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Comparison of outcomes between rectal squamous cell carcinoma and adenocarcinoma.

Large, population-based analyses of rectal squamous cell carcinoma (SCC) have not been previously conducted. We assessed patterns of care, prognostic factors, and outcomes of rectal SCC and adenocarcinoma (AC) in population-based cohorts. Surveillance, Epidemiology, and End Results (SEER) registry searches were performed (1998-2011), producing 42,308 nonmetastatic rectal cancer patients (999 SCC and 41,309 AC). Patient, tumor, and treatment characteristics were compared. Based on risk factors, SCC/AC groups were subdivided into low-, intermediate-, and high-risk groups. Overall survival (OS) was compared between histological and risk groups using Kaplan-Meier method and log-rank test. Multivariate logistic regression models evaluated prognostic factors for 5-year survival. Cox regression modeling was performed on propensity-matched data. Rectal SCC, more common in females and associated with larger tumors of higher grade, was more often treated with radiotherapy (RT) than surgery. Surgery was associated with higher OS in AC but not SCC, and RT had proportionally greater benefits in SCC. These effects of RT and surgery were retained when stratified into risk groups (particularly high/intermediate-risk). Favorable prognostic factors for survival included younger age, non-black race, SCC histology, size ≤3.9 cm, localized stage, lower grade, surgery, and RT. For SCC, race, tumor grade, and surgery were not prognostic factors for survival. Cox regression modeling of propensity-matched data showed that AC histology increased risk of death versus SCC. In the largest analysis of rectal SCC to date, and in the notable absence (and unlikelihood) of prospective data, nonsurgical and RT-based treatment is recommended.

Predictors of survival in contemporary practice after initial radiosurgery for brain metastases.

PURPOSE: The number of brain metastases (BM) is a major consideration in determining patient eligibility for stereotactic radiosurgery (SRS), but the evidence for this popular practice is equivocal. The purpose of this study was to determine whether, following multivariate adjustment, the number and volume of BM held prognostic significance in a cohort of patients initially treated with SRS alone. METHODS AND MATERIALS: A total of 251 patients with primary malignancies, including non-small cell lung cancer (34%), melanoma (30%), and breast carcinoma (16%), underwent SRS for initial treatment of BM. SRS was used as the sole management (62% of patients) or was combined with salvage treatment with SRS (22%), whole-brain radiation therapy (WBRT; 13%), or resection (3%). Median follow-up time was 9.4 months. Survival was determined using the Kaplan-Meier method. Cox regression was used to assess the effects of patient factors on distant brain failure (DBF), local control (LC), and overall survival (OS). RESULTS: LC at 1 year was 94.6%, and median time to DBF was 10 months. Median OS was 11.1 months. On multivariate analysis, statistically significant predictors of OS were presence of extracranial disease (hazard ratio [HR], 4.2, P<.001), total tumor volume greater than 2 cm(3) (HR, 1.98; P<.001), age ≥60 years (HR, 1.67; P=.002), and diagnosis-specific graded prognostic assessment (HR, 0.71; P<.001). The presence of extracranial disease was a statistically significant predictor of DBF (HR, 2.15), and tumor volume was predictive of LC (HR, 4.56 for total volume >2 cm(3)). The number of BM was not predictive of DBF, LC, or OS. CONCLUSIONS: The number of BM is not a strong predictor for clinical outcomes following initial SRS for newly diagnosed BM. Other factors including total treatment volume and systemic disease status are better determinants of outcome and may facilitate appropriate use of SRS or WBRT.

Validation of Recursive Partitioning Analysis and Diagnosis-Specific Graded Prognostic Assessment in patients treated initially with radiosurgery alone.

OBJECT: Brain metastases present a therapeutic challenge because patients with metastatic cancers live longer now than in the recent past due to systemic therapies that, while effective, may not penetrate the blood-brain barrier. In the present study the authors sought to validate the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA), a new prognostic index that takes into account the histological characteristics of the primary tumor, and the Radiation Therapy Ontology Group Recursive Partitioning Analysis (RPA) system by using a single-institution database of patients who were treated initially with stereotactic radiosurgery (SRS) alone for brain metastases. METHODS: Investigators retrospectively identified adult patients who had undergone SRS at a single institution, MD Anderson Cancer Center, for initial treatment of brain metastases between 2003 and 2010 but excluded those who had undergone craniotomy and/or whole-brain radiation therapy at an earlier time; the final number was 251. The Leksell Gamma Knife was used to treat 223 patients, and a linear accelerator was used to treat 28 patients. The patient population was grouped according to DS-GPA scores as follows: 0-0.5 (7 patients), 1 (33 patients), 1.5 (25 patients), 2 (63 patients), 2.5 (14 patients), 3 (68 patients), and 3.5-4 (41 patients). The same patients were also grouped according to RPA classes: 1 (24 patients), 2 (216 patients), and 3 (11 patients). The most common histological diagnoses were non-small cell lung cancer (34%), melanoma (29%), and breast carcinoma (16%). The median number of lesions was 2 (range 1-9) and the median total tumor volume was 0.9 cm(3) (range 0.3-22.9 cm(3)). The median radiation dose was 20 Gy (range 14-24 Gy). Stereotactic radiosurgery was performed as the sole treatment (62% of patients) or combined with a salvage treatment consisting of SRS (22%), whole-brain radiation therapy (12%), or resection (4%). The median duration of follow-up was 9.4 months. RESULTS: In this patient group the median overall survival was 11.1 months. The DS-GPA prognostic index divided patients into prognostically significant groups. Median survival times were 2.8 months for DS-GPA Scores 0-0.5, 3.9 months for Score 1, 6.6 months for Score 1.5, 12.9 months for Score 2, 11.9 months for Score 2.5, 12.2 months for Score 3, and 31.4 months for Scores 3.5-4 (p < 0.0001). In the RPA groups, the median overall survival times were 38.8 months for Class 1, 9.4 months for Class 2, and 2.8 months for Class 3 (p < 0.0001). Neither the RPA class nor the DS-GPA score was prognostic for local tumor control or new lesion-free survival. A multivariate analysis revealed that patient age > 60 years, Karnofsky Performance Scale score ≤ 80%, and total lesion volume > 2 cm(3) were significant adverse prognostic factors for overall survival. CONCLUSIONS: Application of the DS-GPA to a database of patients with brain metastases who were treated with SRS appears to be valid and offers additional prognostic refinement over that provided by the RPA. The DS-GPA may also allow for improved selection of patients to undergo initial SRS alone and should be studied further.