Pectoralis major myofascial interposition flap prevents postoperative pharyngocutaneous fistula in salvage total laryngectomy.

Pharyngocutaneous fistula (PCF) is the most cumbersome complication after salvage total laryngectomy (STL) in patients who have been previously irradiated for laryngeal or hypopharyngeal cancer. To assess the fistula rate, risk factors and effects of primary closure with and without pectoralis major myofascial interposition flap (PMMIF) on fistula formation, we conducted a retrospective review. We identified 48 patients from 2004 to 2013 who underwent STL after failure of primary curative (chemo)radiotherapy in laryngeal or hypopharyngeal cancer. Details of risk factors for PCF formation, other postoperative complications and general outcome data were analyzed. Ten (20.8 %) out of 48 patients underwent STL with PMMIF closure. Patient and tumor features were not different between the groups with or without PMMIF closure. PCF rates were 0 and 42.1 % in patients with and without PMMIF, respectively (p = 0.002). Other operative complications were similar. We identified prior neck irradiation to be a risk factor for fistula formation (p = 0.04). Patients without PCF had a statistically significant reduction of average hospital stay (20 vs. 56 days; p = 0.001). Analysis of fistula management revealed 50 % of PCF to be closed secondarily by a pectoralis major myocutaneous flap. Over one-third of fistulae persisted despite attempted surgical closure in some cases. PMMIF is useful to prevent PCF in STL following (chemo)radiotherapy. Neck irradiation during primary treatment is a risk factor for PCF formation

Superior loco-regional control after primary surgery compared to chemo-radiotherapy for advanced stage laryngeal cancer.

OBJECTIVE The optimal strategy to treat loco-regionally advanced squamous cell carcinoma of the larynx (LSCC) remains to be defined. The goal of this single institution retrospective study was to report on oncologic outcome of advanced LSCC treated with curative intent. METHODS Patients diagnosed and treated for stage T3-T4a LSCC between 2001 and 2014 were retrospectively analyzed. Time-to-event endpoints were calculated beginning from the date of histologic diagnosis, which were analyzed with log-rank test and Cox proportional hazard models. RESULTS The cohort was divided into two subgroups: primary radiotherapy with concomitant cisplatin (CRT) (n=30, 38%) and primary surgery (n=48, 62%). Median follow-up was 56 months. Locoregional control (LRC) for the primary surgery and CRT were 95% and 50% in 5 years, respectively (p<0.01). Progression free survival (PFS) for the primary surgery and CRT were 61% and 38% in 5 years, respectively (p=0.23). The overall survival (OS) after primary surgery and CRT in 5 years were 63% vs. 65%, respectively (p=0.93). The 5-years LRC was significantly superior after surgery compared to RT for cT3 primaries (100% vs 50%, p= 0.0022). No significant differences were observed in the remaining subgroups regarding cT stage and PFS or OS. CONCLUSION Our series demonstrated superior LRC after primary surgery followed by risk-adapted adjuvant (C)RT compared to primary CRT in cT3 LSCC, but no significant difference in PFS or OS in locally-advanced LSCC. The optimal patient selection criteria for the ideal treatment for loco-regionally advanced LSCC still needs to be defined

Outcome and patterns of failure after postoperative intensity modulated radiotherapy for locally advanced or high-risk oral cavity squamous cell carcinoma

Background To determine the outcome and patterns of failure in oral cavity cancer (OCC) patients after postoperative intensity modulated radiotherapy (IMRT) with concomitant systemic therapy. Methods All patients with locally advanced (AJCC stage III/IV) or high-risk OCC (AJCC stage II) who underwent postoperative IMRT at our institution between December 2006 and July 2010 were retrospectively analyzed. The primary endpoint was locoregional recurrence-free survival (LRRFS). Secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), acute and late toxicities. Results Overall 53 patients were analyzed. Twenty-three patients (43%) underwent concomitant chemotherapy with cisplatin, two patients with carboplatin (4%) and four patients were treated with the monoclonal antibody cetuximab (8%). At a median follow-up of 2.3 (range, 1.1–4.6) years the 3-year LRRFS, DMFS and OS estimates were 79%, 90%, and 73% respectively. Twelve patients experienced a locoregional recurrence. Eight patients, 5 of which had both a flap reconstruction and extracapsular extension (ECE), showed an unusual multifocal pattern of recurrence. Ten locoregional recurrences occurred marginally or outside of the high-risk target volumes. Acute toxicity grades of 2 (27%) and 3 (66%) and late toxicity grades of 2 (34%) and 3 (11%) were observed. Conclusion LRRFS after postoperative IMRT is satisfying and toxicity is acceptable. The majority of locoregional recurrences occurred marginally or outside of the high-risk target volumes. Improvement of high-risk target volume definition especially in patients with flap reconstruction and ECE might transfer into better locoregional control

Correlation between hematological parameters and PET/CT metabolic parameters in patients with head and neck cancer.

BACKGROUND Systemic inflammation is predictive of the overall survival in cancer patients and is related to the density of immune cells in the tumor microenvironment of cancer, which in turn correlates with 18F -fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) metabolic parameters (MPs). The density of tumor-infiltrating lymphocytes (TILs) in the microenvironment has the potential to be a biomarker that can be used clinically to optimize patient selection in oropharyngeal head and neck squamous cell carcinoma (HNSCC). There is little to no data regarding the association of systemic inflammation with PET/CT-MPs, especially in HNSCC. This study aimed to evaluate the correlation between markers of host inflammation, namely blood neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), with the PET/CT-MPs standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumor, derived from FDG-PET/CT in patients with nonmetastatic (cM0) HNSCC before treatment. We hypothesized that NLR and PLR at baseline are positively correlated with PET/CT-MPs. METHODS A retrospective review of consecutive patients with HNSCC with a pretreatment PET/CT was performed. NLR and PLR were computed using complete blood counts measured within 10 days before the start of any treatment. The correlation between NLR and PLR with PET/CT-MPs was evaluated with Spearman's rho test. RESULTS Seventy-one patients were analyzed. Overall survival (OS) at 1, 2, and 3 years was 86%, 76%, and 68%. PLR was found to be correlated with MTV (rho = 0.26, P = .03) and TLG (rho = 0.28, P = .02) but not with maximum SUV or mean SUV. There was no correlation between NLR and the analyzed PET/CT-MPs. TLG was associated with worse survival in uni- and multivariable analysis, but no other PET/CT-MPs were associated with either OS or disease-specific survival (DSS). NLR and PLR were associated with OS and DSS on uni- and multivariable analysis. CONCLUSIONS In patients with HNSCC before any treatment such as definitive radio (chemo)therapy or oncologic surgery followed by adjuvant RT, baseline PLR correlated with MTV and TLG but not with SUV. NLR was not correlated with any PET/CT-MPs analyzed in our study. Confirmatory studies are needed, and a potential interaction between tumor microenvironment, host inflammation, and FDG-PET/CT measures warrants further investigation

Definitive intensity modulated radiotherapy in locally advanced hypopharygeal and laryngeal squamous cell carcinoma: mature treatment results and patterns of locoregional failure.

PurposeTo assess clinical outcomes and patterns of loco-regional failure (LRF) in relation to clinical target volumes (CTV) in patients with locally advanced hypopharyngeal and laryngeal squamous cell carcinoma (HL-SCC) treated with definitive intensity modulated radiotherapy (IMRT) and concurrent systemic therapy.MethodsData from HL-SCC patients treated from 2007 to 2010 were retrospectively evaluated. Primary endpoint was loco-regional control (LRC). Secondary endpoints included local (LC) and regional (RC) controls, distant metastasis free survival (DMFS), laryngectomy free survival (LFS), overall survival (OS), and acute and late toxicities. Time-to-event endpoints were estimated using Kaplan-Meier method, and univariate and multivariate analyses were performed using Cox proportional hazards models. Recurrent gross tumor volume (RTV) on post-treatment diagnostic imaging was analyzed in relation to corresponding CTV (in-volume, > 95% of RTV inside CTV; marginal, 20¿95% inside CTV; out-volume, < 20% inside CTV).ResultsFifty patients (stage III: 14, IVa: 33, IVb: 3) completed treatment and were included in the analysis (median follow-up of 4.2 years). Three-year LRC, DMFS and overall survival (OS) were 77%, 96% and 63%, respectively. Grade 2 and 3 acute toxicity were 38% and 62%, respectively; grade 2 and 3 late toxicity were 23% and 15%, respectively. We identified 10 patients with LRF (8 local, 1 regional, 1 local¿+¿regional). Six out of 10 RTVs were fully included in both elective and high-dose CTVs, and 4 RTVs were marginal to the high-dose CTVs.ConclusionThe treatment of locally advanced HL-SCC with definitive IMRT and concurrent systemic therapy provides good LRC rates with acceptable toxicity profile. Nevertheless, the analysis of LRFs in relation to CTVs showed in-volume relapses to be the major mode of recurrence indicating that novel strategies to overcome radioresistance are required

Disease Control With Delayed Salvage Radiotherapy for Macroscopic Local Recurrence Following Radical Prostatectomy

Purpose: To retrospectively assess clinical outcomes and toxicity profile of prostate cancer patients treated with delayed dose-escalated image-guided salvage radiotherapy (SRT) for macroscopic local recurrence after radical prostatectomy (RP).Material and Methods: We report on a cohort of 69 consecutive patients with local recurrence after RP and no evidence of regional or distant metastasis who were referred for salvage radiotherapy between 2007 and 2016. SRT consisted of 64–66 Gy (2 Gy/fraction) to the prostatic bed followed by dose escalation to 72–74 Gy (2Gy/fraction) to the macroscopic disease. All patients received concurrent short-term androgen deprivation therapy (ADT). Biochemical recurrence-free survival (bRFS) and clinical progression-free-survival (cPFS) were depicted using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predictors of survival outcomes. Baseline, acute, and late urinary and gastrointestinal (GI) toxicity rates were reported using CTCAE v4.03.Results: Median time from RP to SRT was 66 months (IQR: 32–124). Median pre-SRT prostate-specific antigen (PSA) was 2.7 ng/ml (IQR: 0.9–6.5). Median follow-up after SRT was 38 months (IQR: 24–66). The 3- and 5-year bRFS were 58 and 44%, respectively. The 3- and 5-year cPFS were 91 and 76%, respectively. Median time from SRT to clinical disease progression was 102 months (IQR 77.5–165). At baseline, 3 patients (4%) had grade 3 urinary symptoms. Six patients (9%) developed acute and six patients (9%) developed late grade 3 urinary toxicity. Five patients (7%) had acute grade 2 GI toxicity. No acute grade 3 GI toxicity was reported. Late grade 3 GI toxicity was reported in one patient (1.5%).Conclusions: Delayed dose-escalated SRT combined with short-course ADT for macroscopic LR after RP was associated with 44% bRFS and 76% cPFS at 5 years. Albeit improved patient stratification is warranted, these data suggest that delayed SRT provides inferior tumor control compared to early intervention

Impact of pretreatment second look 18FDG-PET/CT on stage and treatment changes in head and neck cancer.

Background Patients diagnosed with locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) regularly undergo staging with 18F-FDG PET/CT in our center. In cases of delays in radiotherapy (RT) planning CT more than 4 weeks after initial PET/CT or clinically suspected progress, PET/CT is repeated for restaging and as an RT planning reference. Our aim was to determine the impact of second-look PET/CT on stage migration, treatment change and RT planning. Methods Consequent treatment changes were categorized as minor and major. Minor changes were defined as PET/CT-based modifications of RT plans, e.g., the addition of anatomical compartments, changes in high- and low-risk dose levels or both. Major changes included changes from curative to palliative treatment intent and alterations of interdisciplinary treatment plans, such as the addition of induction chemotherapy, switch to primary surgery, no treatment and/or the necessity of additional diagnostic work-up resulting in the postponement or cancellation of treatment. Results Thirty-two newly diagnosed LAHNSCC patients who were treated between 2014 and 2018 underwent second-look PET/CT (median interval 42.5 days). Second-look PET/CT led to locoregional and distant upstaging in 3/32 and 1/32 patients, respectively. In 1/32 patients (3%), second-look PET/CT led to a palliative approach with systemic treatment. New lymph node metastases were discovered in 16 patients, 6 of whom also showed significant progression of the primary tumor, resulting in minor changes in 16 of the remaining 31 patients (52%) who were treated curatively. Conclusion If RT treatment planning of LAHNSCC was delayed by more than 4 weeks after initial PET/CT staging or when progression was clinically suspected, a second look at 18FDG-PET/CT was performed. This led to changes in treatment planning in more than half of the cases, which is expected to directly influence oncologic outcomes

Incidence of second primary cancers after radiotherapy combined with platinum and/or cetuximab in head and neck cancer patients.

PURPOSE The second primary cancer (SPC) incidence after treatment with platinum-based chemotherapy and cetuximab in combination with radiotherapy has not been previously reported. Our aim was to compare SPC risk following radiotherapy in combination with these agents for the treatment of head and neck squamous cell carcinoma (HNSCC). METHODS The charts of 296 cases treated for loco-regionally advanced HNSCC between 2009 and 2015 were retrospectively reviewed for patient, tumor, and procedural characteristics. All patients were planned to undergo radiotherapy either with platinum compounds (group: Platinum) or monoclonal antibody cetuximab (group: Cetuximab). A third group of patients switched from platinum compounds to cetuximab due to toxicity (group: Switch). Treatment groups were evaluated for the incidence of SPC with log-rank test. Possible confounders were investigated with multivariate Cox's proportional hazards model. All tests were two-sided, and a p < 0.05 was set to indicate statistical significance. RESULTS Median follow-up was 36 months. Platinum, Cetuximab, and Switch groups consisted of 158, 101, and 37 patients, respectively. Three-year overall survival in the whole cohort was 70%. The rate of SPC was comparable between Platinum (9.2%) and Cetuximab (11.5%) groups (p = 0.98), whereas the patients in the Switch group were exposed to a significantly higher incidence of SPC (23.3%) in 3 years (p = 0.01). The multivariate model indicated Switch to be the only variable correlating with an increased risk for SPC. CONCLUSIONS The Switch strategy may expose the patients to an increased risk of developing SPC. The use of switch should be advocated with caution until robust pre-clinical and clinical data are available

Effect of preoperative immunonutrition on complications after salvage surgery in head and neck cancer.

BACKGROUND Patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma are at high risk of postoperative complications due to the adverse effects of radiotherapy on wound healing. Malnutrition is an additional risk factor and we tested the hypothesis that preoperative administration of immunonutrition would decrease complications in this high risk population. METHODS This single armed study with historical control included consecutive patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma. We compared outcomes before and after implementation of preoperative immunonutrition and adjusted the regression analysis for gender, age, body mass index, Nutritional Risk Screening (NRS 2002), tobacco and alcohol consumption, tumor localization, tumor stage, and type of surgery. The primary endpoint was overall complications from surgery within a follow-up of 30 days. RESULTS Ninety-six patients were included (intervention group: 51, control group: 45). Use of preoperative immunonutrition was associated with a significant reduction in overall complications (35% vs. 58%, fully-adjusted odds ratio 0.30 (95%CI 0.10-0.91, p = 0.034). Length of hospital stay was also significantly reduced (17 days vs. 6 days, p = < 0.001). No differences in mortality and hospital readmission were found. These results remained robust in multivariate analysis. CONCLUSIONS In patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma, preoperative immunonutrition exhibited favorable effects on the complication rate and consequently reduced the length of hospital stay. By improving both tissue regeneration and immune response, immunonutrition may help to improve surgical outcomes in this high-risk population

Unplanned hospitalizations in patients with locoregionally advanced head and neck cancer treated with (chemo)radiotherapy with and without prophylactic percutaneous endoscopic gastrostomy.

BACKGROUND Current studies about percutaneous endoscopic gastrostomy (PEG) tube placement report equivalent patient outcomes with prophylactic PEG tubes (pPEGs) versus common nutritional support. Unreported was if omitting a pPEG is associated with an increased risk of complications leading to a treatment-related unplanned hospitalization (TRUH). METHODS TRUHs were retrospectively analyzed in patients with advanced head and neck squamous cell carcinoma (n = 310) undergoing (chemo)radiotherapy with (pPEG) or without PEG (nPEG). RESULTS In 88 patients (28%), TRUH was reported. One of the leading causes of TRUH in nPEG patients was inadequate oral intake (n = 16, 13%), and in pPEG patients, complications after PEG tube insertion (n = 12, 10%). Risk factors for TRUH were poor performance status, tobacco use, and surgical procedures. CONCLUSIONS Omitting pPEG tube placement without increasing the risk of an unplanned hospitalization due to dysphagia, dehydration or malnutrition, is an option in patients being carefully monitored. Patients aged > 60 years with hypopharyngeal carcinoma, tobacco consumption, and poor performance status appear at risk of PEG tube-related complications leading to an unplanned hospitalization