Technical Advances and Pitfalls in Head and Neck Radiotherapy

Intensity Modulated Radiotherapy (IMRT) is the standard of care in the treatment of head and neck squamous cell carcinomas (HNSCC) based on level 1 evidence. Technical advances in radiotherapy have revolutionized the treatment of HNSCC, with the most tangible gain being a reduction in long term morbidity. However, these benefits come with a serious and sobering price. Today, there is a greater chance of missing the target/tumor due to uncertainties in target volume definition by the clinician that is demanded by the highly conformal planning process involved with IMRT. Unless this is urgently addressed, our patients would be better served with the historically practiced non conformal radiotherapy, than IMRT which promises lesser morbidity. Image guided radiotherapy (IGRT) ensures the level of set up accuracy warranted to deliver a highly conformal treatment plan and should be utilized with IMRT, where feasible. Proton therapy has a theoretical physical advantage over photon therapy due to a lack of “exit dose”. However, clinical data supporting the routine use of this technology for HNSCC are currently sparse. The purpose of this article is to review the literature, discuss the salient issues and make recommendations that address the gaps in knowledge

The electronic self report assessment and intervention for cancer: promoting patient verbal reporting of symptom and quality of life issues in a randomized controlled trial

Background: The electronic self report assessment - cancer (ESRA-C), has been shown to reduce symptom distress during cancer therapy The purpose of this analysis was to evaluate aspects of how the ESRA-C intervention may have resulted in lower symptom distress (SD). Methods: Patients at two cancer centers were randomized to ESRA-C assessment only (control) or the Web-based ESRA-C intervention delivered to patients’ homes or to a tablet in clinic. The intervention allowed patients to self-monitor symptom and quality of life (SxQOL) between visits, receive self-care education and coaching to report SxQOL to clinicians. Summaries of assessments were delivered to clinicians in both groups. Audio-recordings of clinic visits made 6 weeks after treatment initiation were coded for discussions of 26 SxQOL issues, focusing on patients’/caregivers’ coached verbal reports of SxQOL severity, pattern, alleviating/aggravating factors and requests for help. Among issues identified as problematic, two measures were defined for each patient: the percent SxQOL reported that included a coached statement, and an index of verbalized coached statements per SxQOL. The Wilcoxon rank test was used to compare measures between groups. Clinician responses to problematic SxQOL were compared. A mediation analysis was conducted, exploring the effect of verbal reports on SD outcomes. Results: 517 (256 intervention) clinic visits were audio-recorded. General discussion of problematic SxQOL was similar in both groups. Control group patients reported a median 75% of problematic SxQOL using any specific coached statement compared to a median 85% in the intervention group (p = .0009). The median report index of coached statements was 0.25 for the control group and 0.31 for the intervention group (p = 0.008). Fatigue, pain and physical function issues were reported significantly more often in the intervention group (all p < .05). Clinicians' verbalized responses did not differ between groups. Patients' verbal reports did not mediate final SD outcomes (p = .41). Conclusions: Adding electronically-delivered, self-care instructions and communication coaching to ESRA-C promoted specific patient descriptions of problematic SxQOL issues compared with ESRA-C assessment alone. However, clinician verbal responses were no different and subsequent symptom distress group differences were not mediated by the patients' reports. Trial registration NCT00852852; 26 Feb 200

PTCOG Head and Neck Subcommittee Consensus Guidelines on Particle Therapy for the Management of Head and Neck Tumors

Purpose: Radiation therapy is a standard modality in the treatment for cancers of the head and neck, but is associated with significant short- and long-term side effects. Proton therapy, with its unique physical characteristics, can deliver less dose to normal tissues, resulting in fewer side effects. Proton therapy is currently being used for the treatment of head and neck cancer, with increasing clinical evidence supporting its use. However, barriers to wider adoption include access, cost, and the need for higher-level evidence.Methods: The clinical evidence for the use of proton therapy in the treatment of head and neck cancer are reviewed here, including indications, advantages, and challenges.Results: The Particle Therapy Cooperative Group Head and Neck Subcommittee task group provides consensus guidelines for the use of proton therapy for head and neck cancer.Conclusion: This report can be used as a guide for clinical use, to understand clinical trials, and to inform future research efforts.</p

Intratumoral Delivery of Plasmid Interleukin-12 Via Electroporation Leads to Regression of Injected and Non-Injected Tumors in Merkel Cell Carcinoma

Purpose: Interleukin-12 (IL12) promotes adaptive type I immunity and has demonstrated antitumor efficacy, but systemic administration leads to severe adverse events (AE), including death. This pilot trial investigated safety, efficacy, and immunologic activity of intratumoral delivery of IL12 plasmid DNA (tavo) via in vivo electroporation (i.t.-tavo-EP) in patients with Merkel cell carcinoma (MCC), an aggressive virus-associated skin cancer. Experimental Design: Fifteen patients with MCC with superficial injectable tumor(s) received i.t.-tavo-EP on days 1, 5, and 8 of each cycle. Patients with locoregional MCC (cohort A, N = 3) received one cycle before definitive surgery in week 4. Patients with metastatic MCC (cohort B, N = 12) received up to four cycles total, administered at least 6 weeks apart. Serial tumor and blood samples were collected. Results: All patients successfully completed at least one cycle with transient, mild (grades 1 and 2) AEs and without significant systemic toxicity. Sustained (day 22) intratumoral expression of IL12 protein was observed along with local inflammation and increased tumor-specific CD8+ T-cell infiltration, which led to systemic immunologic and clinical responses. The overall response rate was 25% (3/12) in cohort B, with 2 patients experiencing durable clinical benefit (16 and 55+ months, respectively). Two cohort A patients (1 with pathologic complete remission) were recurrence-free at 44+ and 75+ months. Conclusions: I.t.-tavo-EP was safe and feasible without systemic toxicity. Sustained local expression of IL12 protein and local inflammation led to systemic immune responses and clinically meaningful benefit in some patients. Gene electrotransfer, specifically i.t.-tavo-EP, warrants further investigation for immunotherapy of cancer