Carl DeSelm

Proton Beam Reirradiation for Recurrent Head and Neck Cancer: Multi-institutional Report on Feasibility and Early Outcomes

PURPOSE Reirradiation therapy (re-RT) is the only potentially curative treatment option for patients with locally recurrent head and neck cancer (HNC). Given the significant morbidity with head and neck re-RT, interest in proton beam radiation therapy (PBRT) has increased. We report the first multi-institutional clinical experience using curative-intent PBRT for re-RT in recurrent HNC. METHODS AND MATERIALS A retrospective analysis of ongoing prospective data registries from 2 hybrid community practice and academic proton centers was conducted. Patients with recurrent HNC who underwent at least 1 prior course of definitive-intent external beam radiation therapy (RT) were included. Acute and late toxicities were assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 and the Radiation Therapy Oncology Group late radiation morbidity scoring system, respectively. The cumulative incidence of locoregional failure was calculated with death as a competing risk. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were calculated with the Kaplan-Meier method. RESULTS Ninety-two consecutive patients were treated with curative-intent re-RT with PBRT between 2011 and 2014. Median follow-up among surviving patients was 13.3 months and among all patients was 10.4 months. The median time between last RT and PBRT was 34.4 months. There were 76 patients with 1 prior RT course and 16 with 2 or more courses. The median PBRT dose was 60.6 Gy (relative biological effectiveness, [RBE]). Eighty-five percent of patients underwent prior HNC RT for an oropharynx primary, and 39% underwent salvage surgery before re-RT. The cumulative incidence of locoregional failure at 12 months, with death as a competing risk, was 25.1%. The actuarial 12-month freedom-from-distant metastasis and overall survival rates were 84.0% and 65.2%, respectively. Acute toxicities of grade 3 or greater included mucositis (9.9%), dysphagia (9.1%), esophagitis (9.1%), and dermatitis (3.3%). There was 1 death during PBRT due to disease progression. Grade 3 or greater late skin and dysphagia toxicities were noted in 6 patients (8.7%) and 4 patients (7.1%), respectively. Two patients had grade 5 toxicity due to treatment-related bleeding. CONCLUSIONS Proton beam re-RT of the head and neck can provide effective tumor control with acceptable acute and late toxicity profiles likely because of the decreased dose to the surrounding normal, albeit previously irradiated, tissue, although longer follow-up is needed to confirm these findings.

CAR T-cell therapy for pancreatic cancer

Chimeric antigen receptor (CAR) T‐cell therapy utilizes genetic engineering to redirect a patients own T cells to target cancer cells. The remarkable results in hematological malignancies prompted investigating this approach in solid tumors such as pancreatic cancer. The complex tumor microenvironment, stromal hindrance in limiting immune response, and expression of checkpoint blockade on T cells pose hurdles. Herein, we summarize the opportunities, challenges, and state of knowledge in targeting pancreatic cancer with CAR T‐cell therapy.

Long-term patterns of relapse and survival following definitive intensity-modulated radiotherapy for non-endemic nasopharyngeal carcinoma.

BACKGROUND We report treatment outcomes for a large non-endemic cohort of patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) and chemotherapy. METHODS We identified 177 consecutive patients with newly diagnosed, non-metastatic nasopharyngeal cancer treated with definitive IMRT between 1998 and 2011. Endpoints included local, regional, distant control, and overall survival. RESULTS Median follow-up was 52months. The 3-/5-year actuarial rates of local control, regional control, distant control, and overall survival were 92%/83%, 93%/91%, 86%/83%, and 87%/74%, respectively. The median time to local recurrence was 30months; the annual hazard of local recurrence did not diminish until the 6th year of follow-up. CONCLUSIONS Overall, we observed excellent rates of disease control and survival consistent with initially reported results from our institution. Attaining locoregional control in patients with extensive primary tumors remains a significant clinical challenge. With mature follow-up we observed that more than half of observed local relapses occurred after 2years, a pattern distinct from that of carcinomas arising from other head and neck sites. These findings raise the possibility that patients with NPC may benefit from close follow-up during post-treatment years 3-5.

Head and Neck Reirradiation

Treatment of locoregional failure, recurrence, or second primary tumor after prior exposure to high-dose (>50 Gy) RT in the head and neck is difficult. If left untreated, the prognosis is very poor, with a median survival of only 5 months [1]. Surgical resection and reirradiation are the only two curative options, and surgical resection is only possible in roughly 20% of patients [2–4]. When feasible, surgery achieves a 5-year overall survival rate of roughly 16–36% [5, 6], and adjuvant radiation is often recommended. Although the timing is sometimes debated, PFS is improved with immediate compared to delayed postoperative reirradiation [7]. Many head and neck cancer-related deaths result from persistent or recurrent locoregional disease, even in the setting of metastatic disease, exemplifying the continued importance of local control [8, 9]. In addition, uncontrolled locoregional disease in the H&N is extremely detrimental to patients’ QOL due to pain, bleeding, foul odor, and unsightly fungating masses. One-year LRC and OS for proton reirradiation from the largest reported series are 70% and 67%, respectively [10]. This compares favorably to photon reirradiation, where retrospective comparison from the same institution showed 1 year LRC and OS of 55% and 59%, respectively [11]. ≤60 Gy is associated with a greater hazard ratio for local failure in the setting of reirradiation [12]. For patients who are poor candidates for full-dose reirradiation, a less aggressive radiation regimen may be offered, known as the “Quad Shot” (3.7 Gy twice daily × 2 days, followed by a 4-week break, repeated up to 3–4 cycles) [13]. This regimen carries less risk and fewer side effects as it allows for response and symptom assessment between courses and provides palliative benefit and potentially local control benefit over no reirradiation [13].