Inversely and adaptively planned interstitial brachytherapy: A single implant approach.

OBJECTIVE: To evaluate the efficacy, feasibility and safety of image-based, inversely and adaptively planned high-dose rate interstitial brachytherapy (HDR-ISBT) to treat advanced primary or recurrent gynecologic malignancy in a single implant, three-consecutive-day regimen. METHODS: Clinical demographics and outcome data were abstracted from all patients with primary and recurrent gynecologic malignancies who received HDR-ISBT boost from 2014 to 2017. Treatment consisted of a single implant (~7 Gy × 4 fractions) of interstitial needles using the Syed-Neblett template over a three-day hospital admission. CT-based (3D) simulation with inverse and adaptive planning was utilized for each fraction. MR prior to and MR immediately after external beam therapy were fused for HDR-ISBT target delineation. RESULTS: Forty women with an overall median follow-up of 18 months (range: 6-54 months) received an HDR-ISBT boost. Of the 30 primary cases (83% cervix, 10% vaginal, 7% uterine), 44% had organ invasion (bladder, rectal or both) on MRI. Median coverage and dose are reported (V100: 98%, HR-CTV EQD2: 85.1 Gy, D90: 92 Gy). A significant association existed between rectal doses exceeding GEC-ESTRO recommendations (D2cc < 75 Gy) and the development of grade 3 gastrointestinal toxicity with a relative risk of 1.4 [1.1-1.8] (p = .046). Actuarial two-year overall survival (OS), local control (LC) and progression-free survival (PFS) were 81%, 81% and 64%, respectively. CONCLUSIONS: A four fraction, inversely and adaptively planned, single-implant approach of image-based HDR-ISBT provides excellent coverage, minimal toxicity and effective local control in patients with advanced and recurrent disease.

Detection of Alteration in Carotid Artery Volumetry Using Standard-of-care Computed Tomography Surveillance Scans Following Unilateral Radiation Therapy for Early-stage Tonsillar Squamous Cell Carcinoma Survivors: A Cross-Sectional Internally-Matched Carotid Isodose Analysis.

Purpose: Radiation induced carotid artery disease (RICAD) is a major cause of morbidity and mortality among survivors of oropharyngeal cancer. This study leveraged standard-of-care CT scans to detect volumetric changes in the carotid arteries of patients receiving unilateral radiotherapy (RT) for early tonsillar cancer, and to determine dose-response relationship between RT and carotid volume changes, which could serve as an early imaging marker of RICAD. Methods and Materials: Disease-free cancer survivors (>3 months since therapy and age >18 years) treated with intensity modulated RT for early (T1-2, N0-2b) tonsillar cancer with pre- and post-therapy contrast-enhanced CT scans available were included. Patients treated with definitive surgery, bilateral RT, or additional RT before the post-RT CT scan were excluded. Pre- and post-treatment CTs were registered to the planning CT and dose grid. Isodose lines from treatment plans were projected onto both scans, facilitating the delineation of carotid artery subvolumes in 5 Gy increments (i.e. received 50-55 Gy, 55-60 Gy, etc.). The percent-change in sub-volumes across each dose range was statistically examined using the Wilcoxon rank-sum test. Results: Among 46 patients analyzed, 72% received RT alone, 24% induction chemotherapy followed by RT, and 4% concurrent chemoradiation. The median interval from RT completion to the latest, post-RT CT scan was 43 months (IQR 32-57). A decrease in the volume of the irradiated carotid artery was observed in 78% of patients, while there was a statistically significant difference in mean %-change (±SD) between the total irradiated and spared carotid volumes (7.0±9.0 vs. +3.5±7.2, respectively, p<.0001). However, no significant dose-response trend was observed in the carotid artery volume change withing 5 Gy ranges (mean %-changes (±SD) for the 50-55, 55-60, 60-65, and 65-70+ Gy ranges [irradiated minus spared]: -13.1±14.7, -9.8±14.9, -6.9±16.2, -11.7±11.1, respectively). Notably, two patients (4%) had a cerebrovascular accident (CVA), both occurring in patients with a greater decrease in carotid artery volume in the irradiated vs the spared side. Conclusions: Our data show that standard-of-care oncologic surveillance CT scans can effectively detect reductions in carotid volume following RT for oropharyngeal cancer. Changes were equivalent between studied dose ranges, denoting no further dose-response effect beyond 50 Gy. The clinical utility of carotid volume changes for risk stratification and CVA prediction warrants further evaluation.

PET/CT: Radiation Therapy Planning in Head and Neck Cancer.

Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) has an integral role in modern radiotherapy planning for most patients with head and neck malignancies. Fluorine-18-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) should guide standard target delineation and has emerging roles in dose and volume modification for escalation/de-escalation and adaptive radiotherapy. This article discusses the integration of PET/CT into radiotherapy planning.

Psychological distress and cognition among long-term survivors of adolescent and young adult cancer in the USA.

BACKGROUND: Patients diagnosed with cancer as adolescent and young adult (AYA) are at risk for a range of long-term psychosocial sequelae, which have been poorly studied. We sought to characterize the prevalence of cognitive dysfunction and psychological distress among long-term AYA cancer survivors. METHODS: Using data from the National Health Interview Survey between 2010 and 2018, multivariable logistic regression analyses defined the association between AYA cancer diagnosis and cognitive dysfunction and psychological distress, as defined by the 6-item Kessler Psychological Distress Scale. Among AYA cancer survivors, the association between psychological distress and cognitive dysfunction was assessed via multivariable logistic regression. RESULTS: Among 230,675 participants, 2646 (1.1%) were AYA cancer survivors diagnosed > 10 years prior to survey administration. Prior AYA cancer diagnosis was associated with greater odds of cognitive dysfunction (AOR 1.61, 95% CI 1.41-1.82; 27.8% vs. 16.4%) and psychological distress (AOR 1.60, 95% CI 1.41-1.83; 26.6 vs. 15.3%) as compared to individuals without a cancer history. Among survey participants reporting a cancer diagnosis, greater psychological distress was associated with greater odds of cognitive dysfunction (AOR 12.31, 95% CI 7.51-20.18 for severe psychological distress) and cognitive dysfunction was associated with having psychological distress (AOR 4.97, 95% CI 3.66-6.73). CONCLUSION: Long-term survivors of AYA cancer have higher rates of cognitive dysfunction and psychological distress as compared to the general population. Additional services addressing psychosocial and neurocognitive issues should be integrated into standard AYA cancer survivorship care. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors should be aware of self-reported high rates of long-term cognitive dysfunction and psychologic distress and actively seek out formal evaluation and services such as mental health counseling.

Patterns of Dose Escalation Among Patients With Esophageal Cancer Undergoing Definitive Radiation Therapy: 2006-2016.

PURPOSE: Although single-institution series suggest potential benefit to dose escalation in definitive radiation therapy for esophageal cancer, randomized trials including intergroup-0123 and the recently presented A Randomized Trial of Dose Escalation in definitive Chemoradiotherapy for patients with Oesophageal cancer (ARTDECO) trial showed no improvement in outcomes with higher radiation therapy dose. As such, there may be significant variation in radiation dose for definitive treatment of esophageal cancer. METHODS AND MATERIALS: The National Cancer Database was used to identify patients who received a diagnosis of nonmetastatic T2+ esophageal cancer between 2006 and 2016 who did not receive definitive surgery and were treated with chemotherapy and radiation therapy doses between 41.4 and 74 Gy. Multivariable logistic regression defined adjusted odds ratios (AORs) of receipt of >50.4 Gy, including year of diagnosis (2006-2013 vs 2014-2016) ∗ histology (squamous cell carcinoma [SCC] vs adenocarcinoma) and year of diagnosis (2006-2013 vs 2014-2016) ∗ disease site (cervical esophagus vs noncervical esophagus) interaction terms, to assess whether the effect of diagnosis year on dose varied by histology and disease site, respectively. RESULTS: Among 14,517 patients, the most common dose was 50.4 Gy, used for 6955 (47.9%) patients. Dose escalation above 50.4 Gy was observed in 4440 (30.6%) patients and declined by year, from 42.2% in 2006 to 23.5% in 2016. Patients with SCC versus adenocarcinoma had higher odds of dose escalation (39.3% vs 23.8%; AOR 1.46; P < .001), as did those with cervical esophageal primaries versus other primary sites (54.9% vs 27.4%; AOR 2.51; P < .001). The effect of later diagnosis year was greater for adenocarcinoma than for SCC (pint = 0.001, AOR 0.54, P < .001 vs AOR 0.71, P < .001) and significant for noncervical esophagus but not cervical esophagus (pint <0.001, AOR 0.56, P < .001 vs AOR 0.95, P = .616). CONCLUSIONS: Dose escalation in definitive chemoradiotherapy for esophageal cancer declined over time, particularly for adenocarcinoma histology and noncervical primary site. Given the recent results of ARTDECO, our findings can serve as a benchmark from which to measure future shifts in practice patterns.

Incompletely treated malignancies of the major salivary gland: Toward evidence-based care.

BACKGROUND: Unexpected malignancy is common in major salivary gland tumors due to variability of workup, creating challenging treatment decisions. The purpose of this study was to define treatment-related outcomes for patients with incompletely treated major salivary gland tumors. METHODS: A retrospective cohort study was completed of patients with incompletely treated major salivary gland tumors. Tumor burden at presentation was established and treatment categorized. The Cox Proportional Hazards model was used to determine predictors of survival and failure. RESULTS: Of the 440 included patients, patients with gross residual or metastatic disease had a worse overall survival (OS; P < .001). Presentation status was an independent predictor of OS on multivariate analysis (gross residual disease adjusted hazard ratio [HRadjusted ] 2.55; 95% confidence interval [CI] 1.20-5.30; metastatic disease HRadjusted 9.53; 95% CI 3.04-27.06). CONCLUSION: Failure to achieve gross total resection during initial surgery resulted in worse OS. Adequate preoperative planning is required for initial surgical management to optimize tumor control and survival.

Patient reported dry mouth: Instrument comparison and model performance for correlation with quality of life in head and neck cancer survivors.

PURPOSE: To identify a clinically meaningful cut-point for the single item dry mouth question of the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). METHODS: Head and neck cancer survivors who had received radiation therapy (RT) completed the MDASI-HN, the University of Michigan Hospital Xerostomia Questionnaire (XQ), and the health visual analog scale (VAS) of the EuroQol Five Dimension Questionnaire (EQ-5D). The Bayesian information criteria (BIC) were used to test the prediction power of each tool for EQ-5D VAS. The modified Breiman recursive partitioning analysis (RPA) was used to identify a cut point of the MDASI-HN dry mouth score (MDASI-HN-DM) with EQ-5D VAS, using a ROC-based approach; regression analysis was used to confirm the threshold effect size. RESULTS: Two-hundred seven respondents formed the cohort. Median follow-up from the end of RT to questionnaire completion was 88 months. The single item MDASI-HN-DM score showed a linear relationship with the XQ composite score (ρ = 0.80, p < 0.001). The MDASI-HN-DM displayed improved model performance for association with EQ-5D VAS as compared to XQ (BIC of 1803.7 vs. 2016.9, respectively). RPA showed that an MDASI-HN-DM score of ≥6 correlated with EQ-5D VAS decline (LogWorth 5.5). CONCLUSION: The single item MDASI-HN-DM correlated with the multi-item XQ and performed favorably in the prediction of QOL. A MDASI-HN-DM cut point of ≥6 correlated with decline in QOL.

Three-dimensional imaging assessment of anatomic invasion and volumetric considerations for chemo/radiotherapy-based laryngeal preservation in T3 larynx cancer.

OBJECTIVES: To investigate the impact of 3-Diminsional (3D) tumor volume (TV) and extent of involvement of primary tumor on treatment outcomes in a large uniform cohort of T3 laryngeal carcinoma patients treated with nonsurgical laryngeal preservation strategies. MATERIALS AND METHODS: The pretreatment contrast-enhanced computed tomography images of 90 patients with T3 laryngeal carcinoma were reviewed. Primary gross tumor volume (GTVp) was delineated to calculate the 3D TV and define the extent of invasion. Cartilage and soft tissue involvement was coded. The extent of invasion was dichotomized into non/limited invasion versus multiple invasion extension (MIE), and was subsequently correlated with survival outcomes. RESULTS: The median TV was 6.6 cm3. Sixty-five patients had non/limited invasion, and 25 had MIE. Median follow-up for surviving patients was 52 months. The 5-year local control and overall survival rates for the whole cohort were 88% and 68%, respectively. There was no correlation between TV and survival outcomes. However, patients with non/limited invasion had better 5-year local control (LC) than those with MIE (95% vs 72%, p = .009) but did not have a significantly higher rate of overall survival (OS) (74% vs 67%, p = .327). In multivariate correlates of LC, MIE maintained statistical significance whereas baseline airway status showed a statistically significance trend with poor LC (p = .0087 and 0.06, respectively). Baseline good performance status was an independent predictor of improved OS (p = .03) in multivariate analysis. CONCLUSION: The extent of primary tumor invasion is an independent prognostic factor of LC of the disease after definitive radiotherapy in T3 larynx cancer.

Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old.

BACKGROUND: Given the potential for older patients to experience exaggerated toxicity and symptoms, this study was performed to characterize patient reported outcomes in older patients following definitive radiation therapy (RT) for oropharyngeal cancer (OPC). METHODS: Cancer-free head and neck cancer survivors (>6 months since treatment completion) were eligible for participation in a questionnaire-based study. Participants completed the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN). Those patients ≥65 years old at treatment for OPC with definitive RT were included. Individual and overall symptom severity and clinical variables were analyzed. RESULTS: Of the 79 participants analyzed, 82% were male, 95% white, 41% T3/4 disease, 39% RT alone, 27% induction chemotherapy, 52% concurrent, and 18% both, and 96% IMRT. Median age at RT was 71 yrs. (range: 65-85); median time from RT to MDASI-HN was 46 mos. (2/3 > 24 mos.). The top 5 MDASI-HN items rated most severe in terms of mean (±SD) ratings (0-10 scale) were dry mouth (3.48 ± 2.95), taste (2.81 ± 3.29), swallowing (2.59 ± 2.96), mucus in mouth/throat (2.04 ± 2.68), and choking (1.30 ± 2.38) reported at moderate-severe levels (≥5) by 35, 29, 29, 18, and 13%, respectively. Thirty-nine % reported none (0) or no more than mild (1-4) symptoms across all 22 MDASI-HN symptoms items, and 38% had at least one item rated as severe (≥7). Hierarchical cluster analysis resulted in 3 patient groups: 1) ~65% with ranging from none to moderate symptom burden, 2) ~35% with moderate-severe ratings for a subset of classically RT-related symptoms (e.g. dry mouth, mucus, swallowing) and 3) 2 pts. with severe ratings of most items. CONCLUSIONS: The overall long-term symptom burden seen in this older OPC cohort treated with modern standard therapy was largely favorable, yet a higher symptom group (~35%) with a distinct pattern of mostly local and classically RT-related symptoms was identified.

Correction to: Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old.

In the original publication [1] the name of author Jeremy M. Aymard was spelled wrong. The original article was updated to rectify this error.