Faculty Bibliography

PURPOSE/OBJECTIVE:Some patients with previously treated, unresectable, recurrent or metastatic head and neck malignancies are not amenable to curative-intent treatment. Here, we investigated the quad-shot (RTOG 8502) regimen of hypofractionated proton radiotherapy (RT) in that patient population. MATERIALS AND METHODS/METHODS:From 2013 to 2015, 26 patients with recurrent or metastatic cancers were treated with palliative proton RT to the head and neck with quad shot (3.7 Gy twice daily for 2 days). Patient characteristics and survival data were reviewed. RESULTS:Seventeen (65%) patients received ≥ 3 quad-shot cycles and 23 (88%) had prior head and neck RT. Overall palliative response was 73% (n = 19). The most common presenting symptom was pain (50%; n = 13), which improved in 85% (n = 22) of all patients. The overall grade-1 acute-toxicity rate was 58% (n = 15), and no acute grade 3 to 5 toxicities were observed. CONCLUSIONS:The proton quad-shot regimen demonstrates favorable palliative response and toxicity profile, even in patients that received prior RT.

BACKGROUND:In the present study, we assessed the effect of prostate gland size on patient-assessed genitourinary and gastrointestinal (GI) quality of life (QOL) after definitive treatment of prostate adenocarcinoma with proton beam therapy. PATIENTS AND METHODS:(volume of organ receiving x Gy), and patient-reported QOL at 6 months. Genitourinary QOL was assessed using the American Urological Association symptom score and EPIC urinary domain score. GI QOL was assessed using the EPIC GI domain score. RESULTS:, -0.55; P = .67). CONCLUSION:Definitive proton beam therapy for prostate cancer to a dose of 79.2 Gy resulted in excellent patient-reported urinary and GI QOL, independently of the baseline prostate size. This single-institution finding should be tested further in a multi-institutional study to confirm the potential limited role of androgen deprivation therapy.

BACKGROUND:We investigated early outcomes for patients receiving chemotherapy followed by consolidative proton therapy (PT) for the treatment of Hodgkin lymphoma (HL). PATIENTS AND METHODS/METHODS:From June 2008 through August 2015, 138 patients with HL enrolled on either IRB-approved outcomes tracking protocols or registry studies received consolidative PT. Patients were excluded due to relapsed or refractory disease. Involved-site radiotherapy field designs were used for all patients. Pediatric patients received a median dose of 21 Gy(RBE) [range 15-36 Gy(RBE)]; adult patients received a median dose of 30.6 Gy(RBE) [range, 20-45 Gy(RBE)]. Patients receiving PT were young (median age, 20 years; range 6-57). Overall, 42% were pediatric (≤18 years) and 93% were under the age of 40 years. Thirty-eight percent of patients were male and 62% female. Stage distribution included 73% with I/II and 27% with III/IV disease. Patients predominantly had mediastinal involvement (96%) and bulky disease (57%), whereas 37% had B symptoms. The median follow-up was 32 months (range, 5-92 months). RESULTS:The 3-year relapse-free survival rate was 92% for all patients; it was 96% for adults and 87% for pediatric patients (P = 0.18). When evaluated by positron emission tomography/computed tomography scan response at the end of chemotherapy, patients with a partial response had worse 3-year progression-free survival compared with other patients (78% versus 94%; P = 0.0034). No grade 3 radiation-related toxicities have occurred to date. CONCLUSION/CONCLUSIONS:Consolidative PT following standard chemotherapy in HL is primarily used in young patients with mediastinal and bulky disease. Early relapse-free survival rates are similar to those reported with photon radiation treatment, and no early grade 3 toxicities have been observed. Continued follow-up to assess late effects is critical.

Craniospinal irradiation is standard radiotherapy (RT) for localized intracranial nongerminoma germ cell tumors (NGGCT). Given its toxicity, there is interest in using smaller fields. We examined outcomes of NGGCT patients receiving reduced-volume RT at a single institution. Records of 16 patients who received reduced-volume RT as part of definitive treatment between 1996 and 2016 were reviewed. Median age at presentation was 10.8 years (range 4.6-41.0 years). Ten patients had pineal tumors and 6 had suprasellar tumors. All received chemotherapy and 9 patients received second-look surgery thereafter. RT volume was tumor-only to a median of 54 Gy (range 50.4-54 Gy) in 3 patients and whole-ventricle irradiation to a median of 30.6 Gy (range 30.6-36 Gy) with a boost to 54 Gy in 13 patients. Median follow-up was 4.1 years (range 1.9-19.3 years). Three patients recurred locally at a median 9.9 months (range 9.6-10.6 months) after diagnosis, and one of these developed leptomeningeal relapse after 30 months. One patient expired from disease 2.6 years post-diagnosis and another due to stroke 19.3 years post-diagnosis. Fourteen patients are alive with no evidence of disease. Kaplan-Meier estimates of the 4-year overall survival and failure-free survival are 92% (95% confidence interval [CI], 57-99%) and 81% (95% CI 53-94%), respectively. Excellent disease control was observed in these patients with no initial relapses outside of these RT fields. The results of ACNS1123 may better delineate patterns of failure and identify subgroups likely to benefit from this approach.

Use of proton beam therapy has expanded, with the number of proton centres rapidly increasing not only in the USA but also worldwide. The physical characteristics of the proton beam offer important advantages versus widely used photon techniques in terms of radiation precision. In head and neck cancer in particular, proton beam therapy is uniquely suited for the complex anatomy of tumours and sensitive surrounding organs. De-intensification and personalisation of treatment to limit toxicity are of renewed importance in the context of human papilloma virus-associated disease, in which young patients will be cured but bear the consequences of adverse effects for decades. Comparisons of radiation dose distributions between photon and proton techniques suggest considerable benefit in terms of toxicity sparing, but this has only recently been confirmed by substantial clinical data. In this Review, we attempt to define the role of this method in the contemporary multidisciplinary management of various types of head and neck cancer.

AIM/OBJECTIVE:Anterior-oblique (AO) proton beams can form an attractive option for prostate patients receiving external beam radiotherapy (EBRT) as they avoid the femoral heads. For a cohort with hydrogel prostate-rectum spacers, we asked whether it was possible to generate AO proton plans robust to end-of-range elevations in linear energy transfer (LET) and modeled relative biological effectiveness (RBE). Additionally we considered how rectal spacers influenced planned dose distributions for AO and standard bilateral (SB) proton beams versus intensity-modulated radiotherapy (IMRT). MATERIAL AND METHODS/METHODS:We studied three treatment strategies for 10 patients with rectal spacers: (A) AO proton beams, (B) SB proton beams and (C) IMRT. For strategy (A) dose and LET distributions were simulated (using the TOPAS Monte Carlo platform) and the McNamara model was used to calculate proton RBE as a function of LET, dose per fraction, and photon α/β. All calculations were performed on pretreatment scans: inter- and intra-fractional changes in anatomy/set-up were not considered. RESULTS:For 9/10 patients, rectal spacers enabled generation of AO proton plans robust to modeled RBE elevations: rectal dose constraints were fulfilled even when the variable RBE model was applied with a conservative α/β = 2 Gy. Amongst a subset of patients the proton rectal doses for the planning target volume plans were remarkably low: for 2/10 SB plans and 4/10 AO plans, ≤10% of the rectum received ≥20 Gy. AO proton plans delivered integral doses a factor of approximately three lower than IMRT and spared the femoral heads almost entirely. CONCLUSION/CONCLUSIONS:Typically, rectal spacers enabled the generation of anterior beam proton plans that appeared robust to modeled variation in RBE. However, further analysis of day-to-day robustness would be required prior to a clinical implementation of AO proton beams. Such beams offer almost complete femoral head sparing, but their broader value relative to IMRT and SB protons remains unclear.

A 33-year-old man with symptomatic, unresectable osteosarcoma of the neck experienced disease progression despite treatment with multiple systemic agents. Given the tumor location, adjacent to the spinal cord and encasing the brachial plexus, proton beam therapy was recommended instead of conventional photon radiation therapy. The treatment was delivered in 3 weekly 10 cobalt-gray equivalents fractions, and there was minimal associated toxicity. There has been significant improvement in the patient's presenting symptoms as well as radiologically stable disease at 1 year. A photon intensity-modulated radiation therapy plan was created retrospectively for dosimetric comparison and demonstrated noninferiority, thereby highlighting the need for judicious use of proton therapy in certain cases.