A multi‐institution pooled analysis of gastrostomy tube dependence in patients with oropharyngeal cancer treated with definitive intensity‐modulated radiotherapy

Setton, J.; Lee, Nancy Y.; Riaz, Nadeem; Huang, Shaohui; Waldron, John; O’Sullivan, Brian; Zhang, Zhigang; Shi, Weij; Rosenthal, David I.; Hutcheson, Katherine A.; Garden, Adam S.

doi:10.1002/cncr.29022

Cited by 115 publications

(96 citation statements)

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“…Setton et al performed a multiinstitutional analysis of gastrostomy use in patients with oropharyngeal cancer treated with IMRT. 12 While the incidence of 1-year gastrostomy dependence was 8.8% for stage III and IV patients treated with chemoradiation, the incidence was only 5% for patients with T1-2/N0-2 disease. Furthermore, gastrostomy tube dependence increased with smoking.…”

Section: Discussionmentioning

confidence: 93%

Radiation therapy (with or without neck surgery) for phenotypic human papillomavirus–associated oropharyngeal cancer

Garden

Fuller

Rosenthal

et al. 2016

Cancer

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Background Favorable outcomes for HPV-associated oropharyngeal cancer (OPC) has led to interest in identifying a subgroup of patients with the lowest risk of disease recurrence following therapy. De-intensification of therapy for this group may result in survival outcomes that are similar to current therapy but with less toxicity. To advance this effort, we analyzed the outcomes of OPC patients treated with and without systemic therapy. Methods This is a retrospective study of oropharyngeal cancer patients treated between 1985–2012. Criteria for inclusion were ≤ 10 pack-years of cigarette smoking and stage III and IVA limited to T1-3, N1-N2b and T3N0. Survival analysis was performed with the primary endpoint of progression-free survival (PFS). Results The cohort included 857 patients. Systemic therapy was given to 439 patients (51%). Median survival was 80 months. The 2-year PFS rates was 91%. Limiting analysis to 324 patients irradiated without systemic therapy, the 2- and 5- year PFS rates were 90% and 85%, respectively. Further, for these 324 patients the 5- year PFS rates for T1, T2, and T3 disease were 90%, 83%, and 70%, respectively. The 5-year PFS rate for patients treated with systemic therapy for T3 disease was 77% (p = .07). Conclusions Using the low-risk definition currently established in cooperative trials, our patients had a 2-year PFS rates approximating 90%. When evaluating patients treated with radiation alone, we did not observe a compromise in this high rate of PFS, which is higher than the 2-year PFS thresholds used in current cooperative trials.

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Section: Discussionmentioning

confidence: 93%

Radiation therapy (with or without neck surgery) for phenotypic human papillomavirus–associated oropharyngeal cancer

Garden

Fuller

Rosenthal

et al. 2016

Cancer

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“…[23, 24] [2] Despite IMRT’s ability to reduce xerostomia, patients still experience dental caries, swallowing difficulties, osteoradionecrosis, and strictures leading to percutaneous gastrostomy tube(PEG) dependence. [25, 26]…”

Section: Discussionmentioning

confidence: 99%

Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally Advanced Human Papillomavirus–Related Oropharyngeal Carcinoma

Lee

Schöder

Beattie

et al. 2016

International Journal of Radiation Oncology*Biology*Physics

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BACKGROUND Human papilloma virus(HPV)-associated oropharyngeal cancer(OPC) treated with chemoradiation has an excellent prognosis leading to the question of whether de-escalated radiotherapy can result in a similar outcome. Hypoxia is a known negative prognostic factor for OPC. A prospective multi-arm IRB #)-070 study using functional imaging to assess pre/intra-treatment hypoxia for all head and neck cancer is currently on-going. A subset study of this large multi-arm study was designed to test functional imaging response as a selection criteria for de-escalation to gross nodal disease in HPV-associated OPC patients receiving concurrent chemoradiation. METHODS Patients with HPV-positive oropharyngeal carcinoma were enrolled on an IRB approved prospective study of which de-escalation based on imaging response was done for node(s) only. Pretreatment 18F-FDG (Fluorodeoxyglucose) and dynamic 18F-FMISO(fluoromisonidazole) positron emission PET were performed. For patients with pretreatment hypoxia on18F-FMISO PET(defined >1.2 tumor to muscle standard uptake value ratio), a repeat scan was done one week after chemoradiation. Patients without pretreatment hypoxia or with resolution of hypoxia on repeat scan received a 10 Gy dose reduction to metastatic lymph node(s). The 2-year local, regional, distant metastasis(DM)-free, and overall survival(OS) rates were estimated using the Kaplan-Meier product-limit method. A subset of patients had biopsy of a hypoxic node done under image-guidance. RESULTS 33 HPV+ OPC patients were enrolled in this pilot study. 100% showed pre-treatment hypoxia[at primary site and/or node(s)] and among these, 48% resolved[at primary site and/or node(s)] 30% met criteria and received 10Gy reduction to the lymph node(s). At the median follow-up of 32 months[21–61 months], the 2-year locoregional control was 100%. One patient failed distantly with persistence of hypoxia on 18F-FMISO PET. The 2-year DM-free rate was 97%. The 2-year OS rate was 100%. Hypoxia on imaging was confirmed pathologically. CONCLUSIONS Hypoxia is present in HPV+ tumors, but resolves within 1 week of treatment in 48% of cases either at the primary site and/or Lymph node(s). Our 100% locoregional control suggests that intra-treatment functional imaging used to selectively de-escalate node(s) to 60Gy was confirmed safe using our stringent imaging criteria. Intra-treatment functional imaging warrants further study to determine its ultimate role in de-escalation treatment strategies.

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“…The two endpoints in this study (freedom from gastrostomy tube dependence after treatment, and late observer-rated late dysphagia) have both been commonly used as indicators of dysphagia after radiation therapy [2, 4, 22]. The results for the two endpoints differed somewhat.…”

Section: Discussionmentioning

confidence: 98%

Contribution of submandibular gland and swallowing structure sparing to post-radiation therapy PEG dependence in oropharynx cancer patients treated with split-neck IMRT technique

et al. 2016

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BackgroundRadiation therapy-related dysphagia is worsened by xerostomia. The submandibular glands (SMG) produce saliva rich in lubricating mucins, and sparing the SMG has been shown to reduce xerostomia. The goal of this study was to determine whether SMG sparing IMRT is associated with reduced post-treatment PEG dependence in locally advanced oropharynx cancer patients.MethodsPatients treated with definitive radiation therapy for oropharynx cancer were included in this retrospective study. Those with disease recurrence were excluded. Salivary glands and swallowing-related organs at risk, including pharyngeal constrictors, were contoured. Primary endpoint was time from end of radiation treatment to freedom from gastrostomy (PEG) tube dependence. Cox proportional hazards regression and logistic regression were used to assess influence of normal tissue doses on swallowing related endpoints.ResultsSixty-nine patients were included. All had stage III/IV disease and 97% received concurrent systemic therapy. Fifty-seven percent had contralateral SMG (cSMG) mean dose <50 Gy, a level shown to predict for xerostomia. Eighty four percent of patients had a PEG tube placed electively. On univariate analysis, the strongest predictor of time to freedom from PEG tube dependence was cSMG dose (HR 0.97 per Gy (95% CI 0.95–0.98), p < 0.0001). This relationship persisted on multivariate analysis (p = 0.052). The dose to superior and middle pharyngeal constrictor muscles, and larynx were also significant on univariate analysis. Patients with cSMG dose less than median (42 Gy, n = 34) had a significantly shorter time to freedom from PEG dependence: median 1.9 vs. 3.5 months, p < 0.0001. At 6 months, 3% of patients with cSMG dose < 42 Gy were PEG dependent compared to 31% with cSMG dose > 42 Gy (p = 0.002).ConclusionsPatients treated with cSMG sparing radiotherapy had significantly shorter time to PEG tube removal after treatment, suggesting a clinically meaningful reduction in subacute dysphagia compared to non-cSMG sparing treatment.

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A multi‐institution pooled analysis of gastrostomy tube dependence in patients with oropharyngeal cancer treated with definitive intensity‐modulated radiotherapy

Cited by 115 publications

References 30 publications

Radiation therapy (with or without neck surgery) for phenotypic human papillomavirus–associated oropharyngeal cancer

Radiation therapy (with or without neck surgery) for phenotypic human papillomavirus–associated oropharyngeal cancer

Strategy of Using Intratreatment Hypoxia Imaging to Selectively and Safely Guide Radiation Dose De-escalation Concurrent With Chemotherapy for Locoregionally Advanced Human Papillomavirus–Related Oropharyngeal Carcinoma

Contribution of submandibular gland and swallowing structure sparing to post-radiation therapy PEG dependence in oropharynx cancer patients treated with split-neck IMRT technique

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