Outcomes following proton therapy for pediatric esthesioneuroblastoma.

BACKGROUND: Pediatric esthesioneuroblastoma (EN) can infiltrate skull base anatomy, presenting challenges due to high radiation doses and pediatric tissue sensitivity. This study reports outcomes of pediatric EN treated with proton radiotherapy (PT). PROCEDURE: Using an IRB-approved prospective outcomes registry, we evaluated patient, tumor, and treatment-related variables impacting disease control and toxicity in pediatric nonmetastatic EN treated with modern multimodality therapy, including PT. RESULTS: Fifteen consecutive patients (median age 16) comprising Kadish stage B (n = 2), C (n = 9), and D (n = 4) tumors were assessed, including six with intracranial involvement, four with cranial nerve deficits, and four with cervical lymphadenopathy. Before radiation, two had subtotal and 13 had gross total resections (endoscopic or craniofacial). Two underwent neck dissection. Eleven received chemotherapy before radiation (n = 5), concurrent with radiation (n = 4), or both (n = 2). Median total radiation dose (primary site) was 66 Gy/CGE for gross disease and 54 Gy/CGE (cobalt Gray equivalent) for microscopic disease. Median follow-up was 4.8 years. No patients were lost to follow-up. Five-year disease-free and overall survival rates were 86% (no local or regional recurrences). Two patients developed vertebral metastases and died. Two required a temporary feeding tube for oral mucositis/dysphagia. Late toxicities included symptomatic retinopathy, major reconstructive surgery, cataracts, chronic otitis media, chronic keratoconjunctivitis, hypothyroidism, and in-field basal cell skin cancer. CONCLUSIONS: A multimodality approach for pediatric EN results in excellent local control. Despite the moderate-dose PT, serious radiation toxicity was observed; further dose and target volume reductions may benefit select patients. Longer follow-up and comparative data from modern photon series are necessary to fully characterize any relative PT advantage.

Long-term outcomes of fractionated proton beam therapy for benign or radiographic intracranial meningioma.

PURPOSE: Benign intracranial meningioma is one of the most common primary brain neoplasms. Proton therapy has been increasingly utilized for nonoperative management of this neoplasm, yet few long-term outcomes studies exist. METHODS: The medical records of a total of 59 patients with 64 lesions were reviewed under a prospective outcomes tracking protocol for histologically proven or radiographically benign meningioma. The patients were treated with proton therapy at the University of Florida Proton Therapy Institute between 2007 and 2019 and given a median dose of 50.4 GyRBE at 1.8 GyRBE (relative biological effectiveness) (range 48.6-61.2 GyRBE) in once-daily treatments. RESULTS: With a median clinical and imaging follow-up of 6.3 and 4.7 years, the rates of 5-year actuarial local progression and cumulative incidence of grade 3 or greater toxicity were 6% (95% confidence interval [CI] 1%-14%), and 2% (95% CI < 1%-15%), respectively. Two patients experienced local progression after 5 years. The 5-year actuarial overall survival rate was 87% (95% CI 74-94%). CONCLUSION: Fractionated PBT up to 50.4 GyRBE is a safe and highly effective therapy for treating benign intracranial meningioma.

Prognostic significance of venous invasion in node-negative head and neck squamous cell carcinoma.

BACKGROUND: Venous invasion (VI) is not frequently evaluated on routine histologic examination of head and neck squamous cell carcinoma (HNSCC), and the prognostic significance is largely unknown. Studies have shown that extramural venous invasion is an adverse prognostic factor in colorectal carcinoma. To our knowledge, this is the first study evaluating the prognostic significance of venous invasion in node-negative (without clinical or pathologic evidence of lymph node involvement) HNSCC, utilizing the elastic stain. METHODS: A total of 105 consecutive lymph node-negative (N0) HNSCC were evaluated for the presence of venous channel invasion by tumor utilizing the elastin stain. Clinical, demographic, and follow-up data were recorded. RESULTS: Of 37 patients with venous invasion, 19% had loco-regional recurrence, as opposed to 12% of those without. Univariate analysis revealed statistically significant decreased recurrence-free survival in the presence of venous invasion (log-rank [Mantel-Cox] test P-value .025). CONCLUSION: Identification of VI is greatly aided by elastic stain. In patients with node-negative HNSCC, presence of VI resulted in decreased recurrence-free survival on univariate analysis. The impact of VI as a prognostic marker should be further evaluated.

Proton therapy following induction chemotherapy for pediatric and adolescent nasopharyngeal carcinoma.

PURPOSE: In children treated for nasopharyngeal carcinoma, proton therapy and postchemotherapy target volumes can reduce the radiation dose to developing tissue in the brain and the skull base region. We analyzed outcomes in children with nasopharyngeal carcinoma treated with induction chemotherapy followed by moderate-dose proton therapy. METHODS/MATERIALS: Seventeen patients with nonmetastatic nonkeratinizing undifferentiated/poorly differentiated nasopharyngeal carcinoma underwent double-scattered proton therapy between 2011 and 2017. Median age was 15.3 years (range, 7-21). The American Joint Committee on Cancer T and N stage distribution included the following: T1, one patient; T2, five patients; T3, two patients; and T4, nine patients; and N1, six patients; N2, nine patients; and N3, two patients. Median radiation dose to the primary target volume and enlarged lymph nodes was 61.2 Gy (range, 59.4-61.2). Uninvolved cervical nodes received 45 Gy (range, 45-46.8). All radiation was delivered at 1.8 Gy/fraction daily using sequential plans. In 11 patients, photon-based intensity-modulated radiotherapy was used for elective neck irradiation to optimize dose homogeneity and improve target conformity. All patients received induction chemotherapy; all but one received concurrent chemotherapy. Five received adjuvant beta-interferon therapy. RESULTS: Median follow-up was 3.0 years (range, 1.6-7.9). No patients were lost to follow-up. Overall survival, progression-free survival, and local control rates were 100%. Fifteen patients developed mucositis requiring enteral feeding (n = 14) or total parenteral nutrition (n = 1) during radiotherapy. Serious late side effects included cataract (n = 1), esophageal stenosis requiring dilation (n = 1), sensorineural hearing loss requiring aids (n = 1), and hormone deficiency (n = 5, including three with isolated hypothyroidism). CONCLUSION: Following induction chemotherapy, moderate-dose proton therapy can potentially reduce toxicity in the brain and skull base region without compromising disease control. However, further follow-up is needed to fully characterize and evaluate any reduction in long-term complications.

Sperm preservation and neutron contamination following proton therapy for prostate cancer study.

BACKGROUND: The present study investigates the impact of scatter dose radiation to the testis on ejaculate and sperm counts from treatment of prostate cancer with passive-scatter proton therapy. MATERIAL AND METHODS: From March 2010 to November 2014, 20 men with low- or intermediate-risk prostate cancer enrolled in an IRB-approved protocol and provided a semen sample prior to passive-scatter proton therapy and 6-12 months following treatment. Men were excluded if they had high-risk prostate cancer, received androgen deprivation therapy, were on alpha blockers (due to retrograde ejaculation) prior to treatment, had baseline sperm count <1 million, or were unable to produce a pre-treatment sample or could not provide a follow-up specimen. Sperm counts of 0 were considered azoospermia and <15 million/ml were classified as oligospermia. RESULTS: Four patients were unable to provide a sufficient quantity of semen for analysis. Among the 16 remaining patients, only one was found to have oligospermia (7 million/ml). There was a statistically significant reduction in semen volume (median, 0.5 ml) and increase in pH (median 0.5). Although not statistically significant, there appeared to be a decline in sperm concentration (median, 16 million/ml), total sperm count (median, 98.5 million), normal morphology (median, 9%), and rapid progressive motility (median, 9.5%). DISCUSSION: Men did not have azoospermia 6-12 months following passive-scatter proton therapy indicating minimal scatter radiation to the testis during treatment. Changes in semen quantity and consistency may occur due to prostate irradiation, which could impact future fertility and/or sexual activity.

A multinational report of technical factors on stereotactic body radiotherapy for oligometastases.

AIM: Oligometastatic cancer is being increasingly managed with aggressive local therapy using stereotactic body radiation therapy (SBRT). However, few guidelines exist. We summarize the results of an international survey reviewing technical factors for extracranial SBRT for oligometastatic disease to guide safe management. MATERIALS & METHODS: Seven high-volume centers contributed. Levels of agreement were categorized as strong (6-7 common responses), moderate (4-5), low (2-3) or no agreement. RESULTS & CONCLUSION: We present the results of a multi-national and multi-institutional survey of technical factors of SBRT for extracranial oligometastases. Key methods including target delineation, prescription doses, normal tissue constraints, imaging and set-up for safe implementation and practice of SBRT for oligometastasis have been identified. This manuscript will serve as a foundation for future clinical evaluations.

Definitive Radiotherapy for Squamous Cell Carcinoma of the Glottic Larynx.

BACKGROUND: Depending on the extent of disease, squamous cell carcinoma (SCC) of the glottis is managed with surgery, radiotherapy (RT), or a combination of these modalities. Patients with advanced disease may receive concomitant chemotherapy in conjunction with definitive or postoperative RT. METHODS: The treatment policies of the University of Florida and patient outcomes are reviewed. RESULTS: The likelihood of cure after RT for carcinoma in situ (Tis) to T2 glottic SCC varies from 70% to 94% depending on tumor stage. Consideration should be given to adding weekly cisplatin for patients with T2b SCC because of the high local recurrence rate after RT alone. The probability of cure is about 65% to 80% for select low-volume (≤ 3.5 cc) T3 to T4 glottic SCC after RT. These patients should be considered for concomitant weekly cisplatin. Higher-volume tumors, particularly those with airway compromise, should be treated with laryngectomy and postoperative RT. CONCLUSION: Definitive RT is an excellent treatment for select patients with laryngeal cancer.

A multi-national report on stereotactic body radiotherapy for oligometastases: Patient selection and follow-up.

Aims Stereotactic body radiotherapy (SBRT) for oligometastases is increasingly used with few evidenced-based guidelines. We conducted a survey to determine patient selection and follow-up practice patterns. Materials and methods Seven institutions from US, Canada, Europe, and Australia that recommend SBRT for oligometastases participated in a 72-item survey. Levels of agreement were categorized as strong (6-7 common responses), moderate (4-5), low (2-3), or no agreement. Results There was strong agreement for recommending SBRT for eradication of all detectable oligometastases with most members limiting the number of metastases to five (range 2-5) and three within a single organ (range 2-5). There was moderate agreement for recommending SBRT as consolidative therapy after systemic therapy. There was strong agreement for requiring adequate performance status and no concurrent chemotherapy. Additional areas of strong agreement included staging evaluations, primary diagnosis, target sites, and follow-up recommendations. Several differences emerged, including the use of SBRT for sarcoma oligometastases, treatment response evaluation, and which imaging should be performed during follow-up. Conclusion Significant commonalities and variations exist for patient selection and follow-up recommendations for SBRT for oligometastases. Information from this survey may serve to help clarify the current landscape.

Long-Term Outcomes Following Definitive or Adjuvant Proton Radiotherapy for Adenoid Cystic Carcinoma.

Purpose: Adenoid cystic carcinoma (ACC) is a rare malignancy accounting for 1% of all head and neck cancers. Treatment for ACC has its challenges and risks, yet few outcomes studies exist. We present long-term outcomes of patients with ACC of the head and neck treated with proton therapy (PT). Materials and Methods: Under an institutional review board-approved, single-institutional prospective outcomes registry, we reviewed the records of 56 patients with de novo, nonmetastatic ACC of the head and neck treated with PT with definitive (n = 9) or adjuvant PT (n = 47) from June 2007 to December 2021. The median dose to the primary site was 72.6 gray relative biological equivalent (range, 64-74.4) delivered as either once (n = 19) or twice (n = 37) daily treatments. Thirty patients received concurrent chemotherapy. Thirty-one patients received nodal radiation, 30 electively and 1 for nodal involvement. Results: With a median follow-up of 6.2 years (range, 0.9-14.7), the 5-year local-regional control (LRC), disease-free survival, cause-specific survival, and overall survival rates were 88%, 85%, 89%, and 89%, respectively. Intracranial extension (P = .003) and gross residual tumor (P = .0388) were factors associated with LRC rates. While the LRC rate for those with a gross total resection was 96%, those with subtotal resection or biopsy alone were 81% and 76%, respectively. The 5-year cumulative incidence of clinically significant grade ≥3 toxicity was 15%, and the crude incidence at the most recent follow-up was 23% (n = 13). Conclusion: This is the largest sample size with the longest median follow-up to date of patients with ACC treated with PT. PT can provide excellent disease control for ACC of the head and neck with acceptable toxicity. T4 disease, intracranial involvement, and gross residual disease at the time of PT following either biopsy or subtotal resection were significant prognostic features for worse outcomes.

International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors.

BACKGROUND: Sinonasal neoplasms, whether benign and malignant, pose a significant challenge to clinicians and represent a model area for multidisciplinary collaboration in order to optimize patient care. The International Consensus Statement on Allergy and Rhinology: Sinonasal Tumors (ICSNT) aims to summarize the best available evidence and presents 48 thematic and histopathology-based topics spanning the field. METHODS: In accordance with prior International Consensus Statement on Allergy and Rhinology documents, ICSNT assigned each topic as an Evidence-Based Review with Recommendations, Evidence-Based Review, and Literature Review based on the level of evidence. An international group of multidisciplinary author teams were assembled for the topic reviews using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format, and completed sections underwent a thorough and iterative consensus-building process. The final document underwent rigorous synthesis and review prior to publication. RESULTS: The ICSNT document consists of four major sections: general principles, benign neoplasms and lesions, malignant neoplasms, and quality of life and surveillance. It covers 48 conceptual and/or histopathology-based topics relevant to sinonasal neoplasms and masses. Topics with a high level of evidence provided specific recommendations, while other areas summarized the current state of evidence. A final section highlights research opportunities and future directions, contributing to advancing knowledge and community intervention. CONCLUSION: As an embodiment of the multidisciplinary and collaborative model of care in sinonasal neoplasms and masses, ICSNT was designed as a comprehensive, international, and multidisciplinary collaborative endeavor. Its primary objective is to summarize the existing evidence in the field of sinonasal neoplasms and masses.

Proton Radiotherapy for Skull-Base Malignancies: Imaging Considerations of Radiotherapy and Complications.

Proton therapy (PT) is a form of highly conformal external-beam radiotherapy used to mitigate acute and late effects following radiotherapy. Indications for treatment include both benign and malignant skull-base and central nervous system pathologies. Studies have demonstrated that PT shows promising results in minimizing neurocognitive decline and reducing second malignancies with low rates of central nervous system necrosis. Future directions and advances in biologic optimization may provide additional benefits beyond the physical properties of particle dosimetry.

Impact of mandated drug monitoring on opioid use during highly conformal radiotherapy for oropharynx cancer.

BACKGROUND: Prescription drug monitoring programs (PDMPs) have proliferated due to increasing opioid-related deaths. We evaluated acute opioid use changes for 64 patients treated with highly conformal radiotherapy (RT) following a state-mandated PDMP. METHODS: Patients receiving proton therapy (PT) (n=40), intensity-modulated RT (IMRT) (n=14), or both (n=10) were divided into preintervention (n=26) and postintervention cohorts (n=38); records were reviewed retrospectively under an institutional review board (IRB)-approved tracking protocol. Dosages prescribed during acute therapy (during RT-3 months post-RT) and patient-reported pain (Defense and Veterans Pain Rating Scale) were endpoints. Dosages were treated as responses in Chi-square tests (three-level ordinal response). RESULTS: Overall, 72% (n=46) received opioids; of which 22% (n=10) of all patients and 10% (n=2) of opioid-naive patients continued analgesic management 3 months post-RT. Median total doses were 975 and 1,025 morphine milligram equivalents (MME) in pre- and postintervention groups, with no significant differences in MME prescribed (P=0.8) or uncontrolled pain (P=0.3). Statistically significant factors were tonsil primaries (P<0.01) and alcohol use (P=0.02). Uncontrolled pain episodes during and post-RT did not vary per cohort (P=0.19). CONCLUSIONS: PDMP use was not associated with management changes in patient-reported acute pain during RT (IMRT or PT). Following highly conformal RT, few patients remained on narcotics 3 months post-RT.

CBCT-Based Dose Monitoring and Adaptive Planning Triggers in Head and Neck PBS Proton Therapy.

PURPOSE: To investigate the feasibility of using cone-beam computed tomography (CBCT)-derived synthetic CTs to monitor the daily dose and trigger a plan review for adaptive proton therapy (APT) in head and neck cancer (HNC) patients. METHODS: For 84 HNC patients treated with proton pencil-beam scanning (PBS), same-day CBCT and verification CT (vfCT) pairs were retrospectively collected. The ground truth CT (gtCT) was created by deforming the vfCT to the same-day CBCT, and it was then used as a dosimetric baseline and for establishing plan review trigger recommendations. Two different synthetic CT algorithms were tested; the corrected CBCT (corrCBCT) was created using an iterative image correction method and the virtual CT (virtCT) was created by deforming the planning CT to the CBCT, followed by a low-density masking process. Clinical treatment plans were recalculated on the image sets for evaluation. RESULTS: Plan review trigger criteria for adaptive therapy were established after closely reviewing the cohort data. Compared to the vfCT, the corrCBCT and virtCT reliably produced dosimetric data more similar to the gtCT. The average discrepancy in D99 for high-risk clinical target volumes (CTV) was 1.1%, 0.7%, and 0.4% and for standard-risk CTVs was 1.8%, 0.5%, and 0.5% for the vfCT, corrCBCT, and virtCT, respectively. CONCLUSION: Streamlined APT has been achieved with the proposed plan review criteria and CBCT-based synthetic CT workflow.

The impact of local control on widespread progression and survival in oligometastasis-directed SBRT: Results from a large international database.

PURPOSE: We investigated the impact of local control (LC) on widespread progression (WSP) and overall survival (OS) in patients treated to all extracranial oligometastases (OMs) at presentation to SBRT in this retrospective review across 6 international centers. MATERIALS/METHODS: Relationships between LC status of SBRT-directed OMs and OS and WSP (>5 new active/untreated lesions) were explored using Cox and Fine-Gray regression models, adjusting for radioresistant histology and pre-SBRT systemic therapy receipt. The association between LC and dosimetric predictors was analyzed with competing risk regression using death as a competing risk and across a wide range of simulated α/ßratios. RESULTS: In total, 1700 OMs in 1033 patients were analyzed, with 25.2% NSCLC, 22.7% colorectal, 12.8% prostate, and 8.1% breast histology. Patients who failed locally in any SBRT-directed OM within 6 mo were at 3.6-fold higher risk of death and 2.7-fold higher risk of WSP compared to those who remained locally-controlled (p < 0.001). Similar associations existed for each duration of LC investigated through 3 yrs post-SBRT. There was no significant difference in risk of WSP or death between patients who failed in a subset of SBRT-treated lesions vs. patients who failed in all lesions. Minimum dose (Dmin) to the GTV/ITV was most predictive of LC when compared to prescription dose, PTV Dmin, and PTV Dmax. Sensitivity analysis for achieving 1-yr LC > 95% found thresholds of 41.2 Gy and 55.2 Gy in 5 fractions for smaller (< 27.7 cc) and larger radioresistant lesions, respectively. CONCLUSION: This large multinational cohort suggests that the duration of LC following OM-directed SBRT strongly correlates with WSP and OS.

Incidence of Rib Fracture following Treatment with Proton Therapy for Breast Cancer.

Purpose: To determine the rib fracture rate in a cohort of patients with breast cancer treated with proton therapy. Patient and Methods: From a prospective database, we identified 225 patients treated with proton therapy between 2012 and 2020 (223 women; 2 men). Clinical and dosimetric data were extracted, the cumulative incidence method assessed rib fracture rate, and Fine-Gray tests assessed prognostic significance of select variables. In-field rib fracture was defined as a fracture that occurred in a rib located within the 10% isodose line. Out-of-field rib fracture was defined as a fracture occurring in a rib location outside of the 10% isodose line. Results: Of the patients, 74% had left-sided breast cancer; 5%, bilateral; and 21%, right-sided. Dual-energy x-ray absorptiometry scans showed normality in 20%, osteopenia in 34%, and osteoporosis in 6% (test not performed in 40%). Additionally, 57% received an aromatase inhibitor. Target volumes were breast ± internal mammary nodes (IMNs) (16%), breast and comprehensive regional lymphatics (32%), chest wall ± IMNs (1%), and chest wall/comprehensive regional lymphatics (51%). Passive-scattered proton therapy was used for 41% of patients, 58% underwent pencil-beam scanning (PBS), and 1% underwent a combination (passive scattering/PBS), with 85% of patients receiving a boost. Median follow-up was 3.1 years, with 97% having >12-month follow-up. The 3-year cumulative in-field rib fracture incidence was 3.7%. Eight patients developed in-field rib fractures (1 symptomatic, 7 imaging identified) for a 0.4% symptomatic rib fracture rate. Median time from radiation completion to rib fracture identification was 1.8 years (fractures were identified within 2.2 years for 7 of 8 patients). No variables were associated with rib fracture on univariate analysis. Three fractures developed outside the radiation field (0.9% cumulative incidence of out-of-field rib fracture). Conclusion: In this series of patients with breast cancer treated with proton therapy, the 3-year rib fracture rates remain low (in-field 3.7%; symptomatic 0.4%). As in photon therapy, the asymptomatic rate may be underestimated owing to a lack of routine surveillance imaging. However, patients experiencing symptomatic rib fractures after proton therapy for breast cancer are rare.

Outcomes for oligometastatic head and neck cancer treated with stereotactic body radiotherapy: Results from an international multi-institutional consortium.

BACKGROUND: We report the results of an international multi-institutional cohort of oligometastatic (OMD) head and neck cancer (HNC) patients treated with SBRT. METHODS: Patients with OMD HNC (≤5 metastases) treated with SBRT between 2008 and 2016 at six institutions were included. Treated metastasis control (TMC), progression-free survival (PFS), and overall survival (OS) were analyzed by multivariable analysis (MVA). RESULTS: Forty-two patients with 84 HNC oligometastases were analyzed. The TMC rate at 1 and 2 years were 80% and 66%, with a median time to recurrence of 10.1 months. The median PFS and OS were 4.7 and 23.3 months. MVA identified a PTV point maximum (BED)10 > 100 Gy as a predictor of improved TMC (HR = 0.31, p = 0.034), and a cumulative PTV > 48 cc as having worse PFS (HR = 2.99, p < 0.001). CONCLUSION: Favorable TMC and OS was observed in OMD HNCs treated with SBRT.

The significance of a marginal excision after preoperative radiation therapy for soft tissue sarcoma of the extremity.

BACKGROUND: Marginal excision of soft tissue sarcoma (STS), defined as resection through the tumor pseudocapsule or surrounding reactive tissue, increases the likelihood of local recurrence and necessitates re-excision or postoperative radiation. However, its impact after preoperative radiation therapy (RT) remains unclear. This study therefore investigated the significance of marginal margins in patients treated with preoperative RT for extremity STS, reporting long-term local control and limb preservation endpoints. METHODS: The records of 317 adults at the University of Florida with nonmetastatic extremity STS treated from 1980 to 2008 with preoperative RT as part of a limb conservation strategy were reviewed. The median follow-up was 4.7 years (8.3 years for living patients). The median tumor size was 10 cm (range, 2-36 cm), and 86% were high grade. The median RT dose was 50.4 Gy (range, 12.5-57.6 Gy). Margins were classified as wide/radical (n = 105), marginal (n = 179), contaminated (n = 15), positive (n = 17), or unknown (n = 1). Endpoints were local control (LC), amputation-free survival (AFS), cause-specific survival (CSS), and overall survival (OS). RESULTS: Five-year CSS and OS rates were 62% and 59%, respectively. Five-year LC and AFS was 93% and 89%, respectively. AFS by margin status was 64%, 83%, 97%, and 92% for positive, contaminated, marginal, and wide/radical margins, respectively (P<.005). Marginal excision following preoperative RT resulted in equivalent LC and AFS compared with wide/radical margins. CONCLUSIONS: Marginal resection after preoperative RT does not compromise LC or AFS in extremity STS. This finding may be related to radiosterilization of tumor cells within the reactive zone following preoperative RT.

A patient alignment solution for lung SBRT setups based on a deformable registration technique.

PURPOSE: In this work, the authors propose a novel registration strategy for translation-only correction scenarios of lung stereotactic body radiation therapy setups, which can achieve optimal dose coverage for tumors as well as preserve the consistency of registrations with minimal human interference. METHODS: The proposed solution (centroid-to-centroidor CTC solution) uses the average four-dimensional CT (A4DCT) as the reference CT. The cone-beam CT (CBCT) is deformed to acquire a new centroid for the internal target volume (ITV) on the CBCT. The registration is then accomplished by simply aligning the centroids of the ITVs between the A4DCT and the CBCT. Sixty-seven cases using 64 patients (each case is associated with separate isocenters) have been investigated with the CTC method and compared with the conventional gray-value (G) mode and bone (B) mode registration methods. Dosimetric effects among the tree methods were demonstrated by 18 selected cases. The uncertainty of the CTC method has also been studied. RESULTS: The registration results demonstrate the superiority of the CTC method over the other two methods. The differences in the D99 and D95 ITV dose coverage between the CTC method and the original plan is small (within 5%) for all of the selected cases except for one for which the tumor presented significant growth during the period between the CT scan and the treatment. Meanwhile, the dose coverage differences between the original plan and the registration results using either the B or G method are significant, as tumor positions varied dramatically, relative to the rib cage, from their positions on the original CT. The largest differences between the D99 and D95 dose coverage of the ITV using the B or G method versus the original plan are as high as 50%. The D20 differences between any of the methods versus the original plan are all less than 2%. CONCLUSIONS: The CTC method can generate optimal dose coverage to tumors with much better consistency compared with either the G or B method, and it is especially useful when the tumor position varies greatly from its position on the original CT, relative to the rib cage.

Elective neck dissection for second primary after previous definitive radiotherapy.

PURPOSE: The aim of this study was to define the role of neck dissection during surgery for patients who have received elective nodal irradiation in the course of treatment for a prior squamous cell carcinoma of the head and neck (SCCHN) and are subsequently diagnosed with a second primary SCCHN. MATERIALS AND METHODS: We reviewed the medical records of 13 patients who received both definitive radiotherapy and elective nodal irradiation for T1-4 N0 M0 SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx who then subsequently developed a metachronous T1-4 N0 M0 SCCHN primary at a new site. All second primary tumors were treated with surgery. Ten of the 13 patients also received an elective neck dissection (END) at that time: 7 unilateral and 3 bilateral. We report the outcomes for the patients in this series. RESULTS: One (8%) of 13 neck dissection specimens was positive in 1 (10%) of 10 patients. The 5-year outcomes were the following: local-regional control, 67%; local control, 77%; disease-free survival, 62%; overall survival, 38%; and cause-specific survival rate, 77%. Six patients experienced treatment-related complications of grade 2 or higher (per Common Terminology Criteria for Adverse Events, version 4). Complications occurred exclusively in patients who received an END. CONCLUSIONS: The risk of occult nodal disease may be low enough to justify omitting an END for a second primary SCCHN in selected patients while maintaining treatment efficacy and reducing patient morbidity. Larger studies on this subject are needed to further address this question.

Treatment of Uveal Melanoma With Radioactive Iodine 125 Implant Compared With Proton Beam Radiotherapy.

OBJECTIVE: To review the current state of radiation therapy for uveal melanoma and compare particle radiation and brachytherapy. PATIENTS AND METHODS: The medical records of 156 patients treated for uveal melanoma between May 30, 2012, and March 16, 2020, were retrospectively reviewed. Treatments consisted of either radioactive iodine 125 implant (RAI) or fractionated proton radiation (proton beam therapy [PBT]). Baseline characteristics were compared using a Wilcoxon rank sum test or χ2 test. Outcomes were compared using Cox proportional hazards regression models or logistic regression models. RESULTS: The median length of follow-up after treatment was 2.7 years (range, 0.5 to 9.0 years). Patients who underwent treatment with RAI were older (median age, 67 vs 59 years; P<.001) and had a lower tumor classification (American Joint Commission on Cancer; P=.001) compared with those who underwent PBT. There was no significant difference between RAI and PBT in the outcomes of liver metastases, death, enucleation, tearing, vision loss, retinal detachment, tumor thickness, conjunctivitis, optic neuropathy, iris neovascularization, or neovascular glaucoma (all P>.05). Patients who underwent RAI treatment had significantly higher risk of diplopia (P<.001), cataract progression (P<.001), and maculopathy (P=.03) compared with those who received PBT. Patients who underwent RAI were at higher risk of eyelash loss (P=.006) compared with the PBT group. CONCLUSION: Treatment with PBT and RAI has similar efficacy; however, there are differences in the adverse outcomes associated with these 2 modalities.