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Palliative radiation is used to relieve pain and bleeding in patients with locally advanced head and neck cancers. Lower doses are utilized to meet normal tissue tolerances, limiting the duration of palliation. Lattice therapy can achieve intratumoral dose escalation while sparing surrounding tissues, but a standard approach does not exist. In this study, we explore the impact of variation in the values and distributions of peak and valley doses in palliative lattice treatment plans. Five-fraction volumetric-arc based (VMAT) lattice plans were generated using a customized Python v3.6 script. For each combination of peak/valley doses and sphere size and spacing, a bounding box was generated around the gross tumor volume (GTV) and divided into equal segments in the x, y, and z planes. Individual spheres were constructed for a given parameter set and those fully encompassed within the target contracted by 2 cm were used to create peak dose targets with values of 30, 40, and 50 Gy. A valley dose of 20 Gy was chosen to match standard dosing for 5-fraction palliative plans and the associated target volumes were generated by subtracting an 8 mm expansion of the peak dose spheres from the overall target volume. Multi-criteria optimization (MCO) was used to generate a final plan. The planning target volume (PTV) was a uniform 3-mm expansion from the GTV. Target volume and OAR dosimetric parameters were analyzed using Mann-Whitney U and Kruskal-Wallis testing. A total of 72 unique plans were evaluated for 4 patients with large GTV sizes ranging from 159 to 413 cm3. The median time to generate an individual plan using the automated script was 20 minutes (IQR, 18 - 23). Median values of mean GTV and PTV doses were 27.9 Gy (IQR, 24.7 - 30.3) and 26.7 Gy (IQR, 23.9 - 29.1), respectively. Further analysis was then limited to plans containing ablative 50 Gy dose spheres. For these 24 plans, mean GTV and PTV doses increased to a median of 31.7 Gy (IQR, 29.6 - 33.3) and 29.6 Gy (IQR, 27.8 - 31.0), respectively. Mean doses to 1, 2, and 4 cm expansions around the GTV for this cohort had median values of 19.5 Gy, 15.1 Gy, and 9.7 Gy, respectively. Median doses to 0.03 cc of mandible, spinal cord, and esophagus were 28.2 Gy (range, 7.0 - 35.7), 14.7 Gy (range, 9.8 - 18.8), and 8.7 Gy (range, 0.8 - 16.2), respectively. Mean GTV dose was dependent on sphere spacing (median 29.9 Gy for 4 cm spacing vs. 33.5 Gy for 3 cm, p<0.001), but not on sphere size (median 31.3 Gy for 2 cm vs. 31.8 Gy for 1.5 cm vs. 31.5 Gy for 1 cm, p = 0.968). VMAT-based lattice planning allows dose escalation to bulky head and neck tumors, including significant coverage with ablative doses while meeting normal tissue constraints. Thus, lattice plans could enhance palliation while reducing toxicity. Mean target coverage is dependent on sphere spacing. Use of automated plan generation could also facilitate clinical application. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Given the historical toxicity of radiotherapy for head & neck cancer, there has been an emphasis on de-escalation for patients with favorable disease features. The use of unilateral radiation to cervical nodes is a prominent de-escalation strategy in well-lateralized tonsil cancers. However, the safety of this approach for patients with AJCC-7 N2b disease was less well-established in the landmark studies guiding its use. The study hypothesis was that unilateral radiation for AJCC-7 T1-2N2b tonsillar cancer results in a low rate of contralateral nodal failure.Materials/methods: This study was a retrospective chart review of 66 patients treated from 2005 to 2016 at two academic institutions. Eligible patients had AJCC-7 T1-2N2b squamous cell carcinoma of the tonsil and were treated with unilateral radiation therapy. The primary endpoint was the rate of contralateral nodal failure at the time of last follow-up. Ipsilateral recurrence rates and overall survival were additional endpoints of interest. When available, data were collected regarding the presence of clinical extracapsular extension (ECE). Human papillomavirus/p16 status was also assessed.Results: The median age at diagnosis was 55.5 years and 53 patients (80.3%) were male. 38 patients (57.6%) had T1 disease and 28 patients (42.4%) had T2 disease based upon AJCC-7 staging. Of the 52 patients who had information on tumor HPV status, all were positive. In regards to systemic therapy, 18 patients (27.3%) had induction therapy, 26 (39.4%) had concurrent therapy, and 4 (6.1%) had both. The median time to last post-radiation follow-up was 80.9 months; 87.9% of patients remained alive at last follow-up and median OS was not reached. Contralateral nodal failure occurred in 2/66 (3.0%) patients at 3.6 and 20.9 months, respectively. Both patients underwent salvage treatment. The first survived an additional 65 months and the second remains alive at last follow-up 37 months after recurrence. Sixteen patients (24.2%) were felt to have extracapsular extension by clinical exam, radiology, or pathology; one of the two contralateral recurrences occurred in this group. Two patients (3%) experienced recurrence at the treated primary site and/or neck. Overall locoregional control at both 2 and 5 years was 93.9% and the median duration of control was not reached.Conclusion: The use of unilateral radiation for AJCC-7 T1-2N2b tonsillar cancer resulted in low rates of contralateral nodal failure. This outcome demonstrates the safety of considering unilateral treatment in patients with a high ipsilateral nodal burden. Further assessments are needed to determine the impact of radiation volume reduction on patient quality of life. [ABSTRACT FROM AUTHOR]

Although unilateral neck irradiation is frequently implemented in patients with well-lateralized stage T1-2 HPV+ tonsillar squamous cell carcinoma (SCC) to minimize toxicity, its role in patients with N2b (AJCC-7 staging) nodal disease remains controversial. We have separately reported on contralateral nodal recurrence risk in patients with N2b disease receiving unilateral neck radiation. The quality-of-life patient reported outcomes (PRO) in these patients have not been previously reported. Our hypothesis was that patients with AJCC 7th edition T1-2 N2b tonsillar squamous cell carcinoma treated with unilateral neck radiation had mild quality-of-life PROs. The PROs of 44 AJCC-7 T1-2 N2b tonsillar squamous cell carcinoma (SCC) patients from two academic institutions treated with definitive, ipsilateral intensity modulation radiation therapy (IMRT) with or without systemic therapy were reviewed retrospectively. PROs were completed using either the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN) at the first institution, or the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module 35 (EORTC QLQ-H&N35) at the second institution. The primary endpoint was the head and neck-related PROs at 2 years after completion of radiation. Twenty-eight of 30 and 4 of 14 patients from the first and second institutions, respectively, met the primary endpoint and were further analyzed. Of these, 34.4% received radiation alone without systemic therapy and 93.7% received ipsilateral-only neck IMRT. The most common head and neck-related PRO was dry mouth at the first and second institutions (64.2% and 100%, respectively); the least common was difficulty with voice or speech at both institutions (14% and 0%, respectively). There were also no reports of mouth pain or soreness, trouble with teeth, opening mouth, or swallowing liquid/pureed food at the second institution. The overall symptom severity for all PRO categories in both modules were in the mild range, with the highest mean score reported for dry mouth: 2.54 out of 10 on MDASI-HN for the first institution and 2.5 out of 4 on EORTC QLQ-H&N35 for the second institution. The rest of the mean scores for the first institution were < 1.5, while the remainder for the second institution were ≤ 2. The locoregional control and overall survival after a median follow-up of 4.5 years were each 100%. We assessed the 2-year quality-of-life PROs for ipsilaterally radiated tonsillar SCC from 2 institutions using either MDASI-HN or EORTC QLQ-H&N35, and most patients reported mild symptom burden. These findings suggest that ipsilateral-only IMRT is well tolerated in patients with AJCC-7 N2b disease and can be safely employed as a de-escalation strategy. [ABSTRACT FROM AUTHOR]

Standard of care (SoC) for eligible patients with unresectable Stage III non-small cell lung cancer (NSCLC) is the PACIFIC regimen, chemoradiotherapy (CRT) followed by durvalumab, with pneumonitis being the most common adverse event leading to treatment discontinuation. ON TRAX was a multicenter, prospective pilot study that evaluated the ability of a multiparametric remote monitoring system to detect early signs of pneumonitis in patients receiving durvalumab. The pilot aimed to enroll 75 patients (from 25 sites) with unresectable stage III NSCLC after CRT, but prior to receiving SoC durvalumab, with no major comorbidities and not on oxygen. Patients were monitored remotely while on durvalumab for up to one year with a platform of mobile devices (FDA-cleared wearable recording continuous SpO2, respiratory rate, pulse, temperature and motion; spirometer for daily lung function; tablet for patient reported outcomes) and digital applications. The primary objective of the study was to identify pneumonitis by grade, with an exploratory objective to develop a longitudinal algorithm that predicts pneumonitis early. After all the data was collected, individual daily pneumonitis risk scores between 0-1 were computed retrospectively using a pre-monitoring baseline score based on established risk factors plus a weighted sum of univariate vital sign and spirometry variables with thresholds optimized based on clinician-confirmed pneumonitis cases. A rolling pneumonitis risk score was calculated by taking the average of daily scores over the prior five days. We used a k-fold (k=3) approach for the training data set and held an additional 20% of the total data points for validation. The pilot was terminated prematurely due to low enrollment during COVID-19 pandemic and low patient retention for the length of the study. Of the 40 enrolled patients (median age 65 years, 60% male, 60% stage IIIA), nine (23%) completed the study and 31 discontinued early (48% due to study closure, 23% withdrawal of consent, 5% device-related AEs), but remained on SoC durvalumab. Median (IQR) length of monitoring was 81 (44-206) days with a total of 76,960 hours of data. Only four patients (10%) experienced pneumonitis while on the study, with three recorded as grade 2 and 1 as grade 3. The best predictive performance of the longitudinal algorithm was observed with the rolling pneumonitis risk score. Setting a threshold of >0.68 for the score yielded 75% sensitivity, 65% specificity and an odds ratio of 5.5 [95% CI: 0.54-58.8] for correctly predicting pneumonitis within two weeks prior to diagnosis. Even with low incidence of on-study pneumonitis, the longitudinal algorithm developed using remote monitoring demonstrated potential in predicting pneumonitis in patients receiving durvalumab post-CRT when their rolling pneumonitis risk score exceeded the threshold. Future research with a larger sample size and longer follow-up is needed for the validation and refinement of the algorithm. [ABSTRACT FROM AUTHOR]