Failure In Head Research Articles

Pectoralis major myocutaneous flap in salvage reconstruction following free flap failure in head and neck cancer surgery.

ObjectiveThis study aimed to compare the results of the pectoralis major myocutaneous (PMM) flap in primary and salvage head and neck cancer surgery.MethodsA total of 160 patients were enrolled in this study. The salvage group consisted of 30 patients who received immediate PMM flap surgery following free flap failure. In the primary group, the PMM flap was primarily chosen for 130 patients. Related information was collected and analysed. The University of Washington (UW)-Quality of Life questionnaire, version 4, was mailed to every patient.ResultsPartial necrosis was significantly lower in the primary group (n = 13, 10.0%) than in the salvage group (n = 7, 23.3%). Surgical site infection was found in 10 (7.8%) patients in the primary group and in six (20.0%) patients in the salvage group. The mean composite quality of life scores were 66.8 ± 20.5 and 66.2 ± 22.1 in the two groups, respectively. Differences in scores for domains of activity, mood, and anxiety were significant. Disease-specific survival and recurrence-free survival rates were not different between the two groups.ConclusionPMM flap salvage reconstruction has a higher complication rate and poorer functional results, but similar survival prognosis, compared with primary surgery.

Radiomic Profiling of Head and Neck Cancer: 18F-FDG PET Texture Analysis as Predictor of Patient Survival.

Background and Purpose The accurate prediction of prognosis and pattern of failure is crucial for optimizing treatment strategies for patients with cancer, and early evidence suggests that image texture analysis has great potential in predicting outcome both in terms of local control and treatment toxicity. The aim of this study was to assess the value of pretreatment 18F-FDG PET texture analysis for the prediction of treatment failure in primary head and neck squamous cell carcinoma (HNSCC) treated with concurrent chemoradiation therapy. Methods We performed a retrospective analysis of 90 patients diagnosed with primary HNSCC treated between January 2010 and June 2017 with concurrent chemo-radiotherapy. All patients underwent 18F-FDG PET/CT before treatment. 18F-FDG PET/CT texture features of the whole primary tumor were measured using an open-source texture analysis package. Least absolute shrinkage and selection operator (LASSO) was employed to select the features that are associated the most with clinical outcome, as progression-free survival and overall survival. We performed a univariate and multivariate analysis between all the relevant texture parameters and local failure, adjusting for age, sex, smoking, primary tumor site, and primary tumor stage. Harrell c-index was employed to score the predictive power of the multivariate cox regression models. Results Twenty patients (22.2%) developed local failure, whereas the remaining 70 (77.8%) achieved durable local control. Multivariate analysis revealed that one feature, defined as low-intensity long-run emphasis (LILRE), was a significant predictor of outcome regardless of clinical variables (hazard ratio < 0.001, P=0.001).The multivariate model based on imaging biomarkers resulted superior in predicting local failure with a c-index of 0.76 against 0.65 of the model based on clinical variables alone. Conclusion LILRE, evaluated on pretreatment 18F-FDG PET/CT, is associated with higher local failure in patients with HNSCC treated with chemoradiotherapy. Using texture analysis in addition to clinical variables may be useful in predicting local control.

Intraoperative hypotension and flap loss in free tissue transfer surgery of the head and neck.

In free flap head and neck reconstructions, hemodynamic management is complicated by the deleterious effects of excessive crystalloid administration. Patients may undergo periods of hypotension or excess fluid administration. The purpose of this study was to present our examination of the hypotheses that intraoperative hypotension and blood pressure lability are associated with increased fluid administration and flap failure. We reviewed the records of 445 patients undergoing head and neck surgery involving free tissue transfer. We used multivariate logistic regression to examine the relationship between hemodynamic variables and flap loss (primary outcome) and other complications. On multivariate analysis, intraoperative hypotension and large-volume fluid administration were associated with flap loss. Neither blood pressure lability nor vasopressor administration was significantly associated to our primary outcome. Intraoperative hypotension is associated to flap failure in head and neck free tissue transfer surgeries, as is large-volume fluid administration.

Late free flap failure in head and neck reconstruction: A systematic review.

Our objectives were to review all reported cases of late flap failure in head and neck surgery and describe any relevant patterns. We conducted a systematic review of all published cases of free flap failure after postoperative day 7 in head and neck surgery from January 1990 to January 2018. Data were collected with respect to flap type, site of reconstruction, reason for failure, and time to failure. A total of 45 cases of late free flap failure in the head and neck were identified. Among the 34 cases in which the necessary data were available for analysis, 50% of late failures occurred between postoperative day 7 and 14. Common reasons for failure were abscess and vascular compromise. We conclude that most late flap failures occur in the second postoperative week. In patients with risk factors for flap failure, close monitoring for up to 14 days after surgery could detect flap compromise before the flap is lost.

EP-1151: Pattern of failure in head and neck cancer patients after RT-CT based on pre-treatment 18F-FDG PET/CT uptake

EP-1151: Pattern of failure in head and neck cancer patients after RT-CT based on pre-treatment 18F-FDG PET/CT uptake

Neutrophil to Lymphocyte Ratio as Biomarkers in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common neoplasm worldwide. Despite advances in treatment for HNSCC, the patient’s survival remains poor. Therefore, in order to improve HNSCC patient’s outcome, it is essential to explore novel biomarkers for predicting response to treatment. Herein, we state that the neutrophil to lymphocyte ratio (NLR) is a biomarker to predict the efficacy of chemoradiotherapy (CRT) in HNSCC patients and to predict the wound healing failure in head and neck reconstruction surgery. Although elevated pretreatment NLR was significantly correlated with poor response to CRT, lower preoperative NLR tended to exhibit a higher occurrence rate of posto-perative wound healing failure in HN reconstruction surgery. Thus, in case which HNSCC patient with lower NLR has remnant tumor after CRT, salvage surgery with microsurgical reconstruction might include a higher occurrence rate of postoperative wound complications than the present. Head and neck surgeons should take care of the possibility.

Evaluation of Reirradiation in Locally Advanced Head and Neck Cancers: Toxicity and Early Clinical Outcomes.

Objectives Locoregional recurrence is the predominant pattern of treatment failure in advanced head and neck cancers. Reirradiation is a useful modality to treat inoperable head and neck cancer patients with recurrent disease. The aim of the present study was to analyze the treatment toxicity and early clinical outcomes in patients undergoing reirradiation. Methods Twenty patients of head and neck cancers with recurrences or second cancers were evaluated. Reirradiation was done using simultaneous integrated boost volumetric modulated arc therapy (SIB VMAT), intensity modulated radiotherapy (IMRT), or conventional radiotherapy using 6MV photons. Dose prescription ranged from 30 to 60 Gy in conventional fractionation. Results Seventeen males and three females were evaluated in this analysis. The median age of patients under study was 56.5 years. At time of analysis 8 patients (40%) had a complete response, 7 patients (35%) had progressive disease, and 25% had partial response or stable disease. Grade III-IV mucositis, dermatitis, xerostomia, dysphagia, and trismus were seen in 20%, 20%, 50%, 35%, and 45% patients, respectively, during retreatment. Patients receiving a radiotherapy dose less than 45 Gy showed a higher incidence of progressive disease (p = 0.01). The median disease-free survival for patients receiving reirradiation dose of ≥46 Gy was 19 ± 3.3 months (median ± S Error) compared to 8 ± 2.61 months for those with a dose prescription less than 45 Gy (p = 0.03). At 18-month follow-up 26% of patients undergoing reirradiation were disease-free. Conclusions Our results show improved tumor control using a prescription of doses ≥46 Gy in retreatment setting.

CT Texture Analysis Potentially Predicts Local Failure in Head and Neck Squamous Cell Carcinoma Treated with Chemoradiotherapy.

The accurate prediction of prognosis and failure is crucial for optimizing treatment strategies for patients with cancer. The purpose of this study was to assess the performance of pretreatment CT texture analysis for the prediction of treatment failure in primary head and neck squamous cell carcinoma treated with chemoradiotherapy. This retrospective study included 62 patients diagnosed with primary head and neck squamous cell carcinoma who underwent contrast-enhanced CT examinations for staging, followed by chemoradiotherapy. CT texture features of the whole primary tumor were measured using an in-house developed Matlab-based texture analysis program. Histogram, gray-level co-occurrence matrix, gray-level run-length, gray-level gradient matrix, and Laws features were used for texture feature extraction. Receiver operating characteristic analysis was used to identify the optimal threshold of any significant texture parameter. We used multivariate Cox proportional hazards models to examine the association between the CT texture parameter and local failure, adjusting for age, sex, smoking, primary tumor stage, primary tumor volume, and human papillomavirus status. Twenty-two patients (35.5%) developed local failure, and the remaining 40 (64.5%) showed local control. Multivariate analysis revealed that 3 histogram features (geometric mean [hazard ratio = 4.68, P = .026], harmonic mean [hazard ratio = 8.61, P = .004], and fourth moment [hazard ratio = 4.56, P = .048]) and 4 gray-level run-length features (short-run emphasis [hazard ratio = 3.75, P = .044], gray-level nonuniformity [hazard ratio = 5.72, P = .004], run-length nonuniformity [hazard ratio = 4.15, P = .043], and short-run low gray-level emphasis [hazard ratio = 5.94, P = .035]) were significant predictors of outcome after adjusting for clinical variables. Independent primary tumor CT texture analysis parameters are associated with local failure in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy.

CT Texture Analysis: Defining and Integrating New Biomarkers for Advanced Oncologic Imaging in Precision Medicine: A Comment on “CT Texture Analysis Potentially Predicts Local Failure in Head and Neck Squamous Cell Carcinoma Treated with Chemoradiotherapy”

The remarkable article by Kuno et al[1][1] in this issue of the American Journal of Neuroradiology raises several questions: Can texture analysis provide reliable biomarkers to predict treatment success in head and neck squamous cell carcinoma (HNSCC)? If so, will the role of the expert clinical

Management of free flap failure in head and neck surgery.

SUMMARYFree flap surgery is overall considered the gold standard in head and neck reconstruction, with a success rate of 95%. The management of a total flap necrosis and which solution, between a pedicled or a second free flap, is safer for a salvage procedure is still controversial. Object of this study is to describe the authors' management of total free flap loss in head and neck reconstruction and compare the choices and results to those reported in the literature. From January 2012 to January 2016, 149 consecutive free flaps were performed at the Maxillo- Facial Operative Unit of the Hospital Casa Sollievo della Sofferenza in San Giovanni Rotondo (Italy) for reconstruction of head and neck defects. Of these, 6 flaps were lost due to a total necrosis. In 5 cases it was decided to harvest a second free flap, and in the remaining patient a temporalis muscle flap was used. All the free salvage flaps were successful, without complications and with a good aesthetic and functional recovery. Analysing the data obtained, and comparing them with those reported in the literature, it can be concluded that a second subsequent free flap can be considered an ideal and safe procedure in salvage surgery.

Patterns of failure in head and neck cancer patients treated with intensity modulated radiation therapy: editorial response

Patterns of failure in head and neck cancer patients treated with intensity modulated radiation therapy: editorial response

Predictability of Recurrence using Immunohistochemistry to delineate Surgical Margins in mucosal Head and Neck Squamous Cell Carcinoma (PRISM-HNSCC): study protocol for a prospective, observational and bilateral study in Australia and India

ObjectivesTreatment failure and poor 5-year survival in mucosal head and neck squamous cell carcinoma (HNSCC) has remained unchanged for decades mainly due to advanced stage of presentation and high rates...

Exploratory study of the association of volumetric modulated arc therapy (VMAT) plan robustness with local failure in head and neck cancer

This work is to show which is more relevant to cause local failures (LFs) due to patient setup uncertainty between the planning target volume (PTV) underdosage and the potential target underdosage subject to patient setup uncertainties in head and neck (H&N) cancer treated with volumetric‐modulated arc therapy (VMAT). Thirteen LFs in 10 H&N patients treated by VMAT were analyzed. Measures have been taken to minimize the chances of insufficient target delineation for these patients and the patients were clinically determined to have LF based on the PET/CT scan results by an experienced radiologist and then reviewed by a second experienced radiation oncologist. Two methods were used to identify the possible locations of LF due to underdosage: (a) examining the standard VMAT plan, in which the underdosed volume in the nominal dose distribution (UVN) was generated by subtracting the volumes receiving the prescription doses from PTVs, and (b) plan robustness analysis, in which in addition to the nominal dose distribution, six perturbed dose distributions were created by translating the CT iso‐center in three cardinal directions by the PTV margin. The coldest dose distribution was represented by the minimum of the seven doses in each voxel. The underdosed volume in the coldest dose distribution (UVC) was generated by subtracting the volumes receiving the prescription doses in the coldest dose distribution from the volumes receiving the prescription doses in the nominal dose distribution. UVN and UVC were subsequently examined for spatial association with the locations of LF. The association was tested using the binominal distribution and the Fisher's exact test of independence. We found that of 13 LFs, 11 were associated with UVCs (P = 0.011), while three were associated with UVNs (P = 0.99). We concluded that the possible target underdosage due to patient setup uncertainties appeared to be a more relevant factor associated with LF in VMAT for H&N cancer than the compromised PTV coverage at least for the patients included in this study.

Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as predictors of wound healing failure in head and neck reconstruction

Conclusions: In microsurgical head and neck reconstruction, a higher rate of post-operative wound complication could be predicted by a lower pre-operative neutrophil ratio (< 64.9%), neutrophil-lymphocyte ratio (NLR) (< 3.5), and platelet-lymphocyte ratio (PLR) (< 160).Objectives: To evaluate the predictor of post-operative wound complications in microsurgical head and neck reconstruction.Methods: Patients who were undergoing tumor ablation and microsurgical reconstruction from April 2011 to March 2014 were analyzed retrospectively. The pre-operative hematological data, age, sex, co-morbidities, body mass index (BMI), adjuvant therapies, smoking, operation time, blood loss, total protein, T-stage, and Anesthesiologists Performance Status (ASA-PS) score were collected. Cases of post-operative wound healing failure were reviewed.Results: One hundred and three consecutive patients were enrolled. Among these, the results of 77 patients who were younger than 70 years of age were analyzed. The distributions of the neutrophil ratio (p = .0005), lymphocyte ratio (p = .0166), monocyte ratio (p = .0341), NLR (p = .005), and PLR (p = .008) differed significantly between the patients with and without post-operative wound healing failure. Neutrophil ratio, NLR, and PLR cut-off values of 64.9, 3.5, and 160 were significantly associated with the rate of wound healing failure rate (p = .0002, .00021, .0042, respectively).

Preliminary results from KEYNOTE-055: Pembrolizumab after platinum and cetuximab failure in head and neck squamous cell carcinoma (HNSCC).

6011Background: Current treatment options for patients (pts) with recurrent/metastatic (R/M) HNSCC who progress on platinum and cetuximab have very limited efficacy. Pembrolizumab, an anti–PD-1 ant...

Elective Nodal Irradiation and Patterns of Failure in Head and Neck Cancer Following Primary Radiation Therapy

Elective Nodal Irradiation and Patterns of Failure in Head and Neck Cancer Following Primary Radiation Therapy

Elective Nodal Irradiation and Patterns of Failure in Head and Neck Cancer After Primary Radiation Therapy

The delineation of elective clinical target volumes in head and neck cancer (HNC) is important; however, the extent of lymph node levels necessary to include is debated. A comprehensive analysis of recurrence patterns in a large cohort of patients with HNC was performed, with an emphasis on recurrence in the retropharyngeal region and level IB. From 2005 to 2012, 942 patients with oropharyngeal, hypopharyngeal, laryngeal or oral cavity carcinomas were curatively treated with primary radiation therapy. The median follow-up period was 34months, and 77% of the patients underwent intensity modulated radiation therapy. The retropharyngeal region was only routinely included in cases of involvement of the posterior pharynx wall and level IB only in cases of involvement of the oral cavity. In patients with regional recurrence, the anatomic site of the recurrence was assessed from the surgical descriptions or computed tomography scans and compared with the original radiation treatment plan (available from 2007 onward). The p16 status was available for 282 oropharynx carcinoma cases, with 65% p16-positive. Of the 942 patients, 376 (40%) developed recurrences: 228 (24.2%) local, 123 (13.1%) regional, and 109 (11.6%) distant. In 700 patients with available treatment plans, retropharyngeal and level IB recurrence was observed in 2 and 7 patients, respectively. Eight patients (1.1%) had recurrence in a lymph node level not included in their primary treatment plan. For oropharynx carcinoma, the locoregional control rate (90% vs 70%) but not distant control rate (92% vs 87%), was significantly better in the p16-positive than in the p16-negative patients. Although fewer recurrences developed in the p16-positive group, patients with recurrence of p16-positive tumors were more likely to develop recurrence in distant sites. Retropharyngeal or level IB recurrence after primary HNC radiation therapy is rare. Thus, inclusion of these regions in the elective treatment volumes should be limited to patients with involvement of the posterior pharyngeal wall or oral cavity.

Suberoylanilide hydroxamic acid (SAHA) reverses chemoresistance in head and neck cancer cells by targeting cancer stem cells via the downregulation of nanog.

Acquisition of chemoresistance and metastatic phenotype are the major causes of treatment failure and mortality in head and neck squamous cell carcinoma (HNSCC) patients. Histone deacetylases (HDACs) have been shown to be overexpressed in many tumor types and directly linked to poor prognosis. In this study, we demonstrate that HDACs are markedly elevated in HNSCC. HDACs expression was further increase in cisplatin resistant cell lines (CisR). In addition, cisplatin-resistant cells showed enhanced stem cell properties and tumor metastasis. Depletion of HDAC1 and 2 in CisR cell lines significantly reversed cisplatin resistance and tumorsphere formation. Next, we tested the efficacy of Suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, by using both in vitro and in vivo models. SAHA significantly inhibited cell proliferation and synergistically enhanced the anti-proliferative effects of cisplatin. In addition, SAHA significantly decreased tumorsphere formation by markedly reducing nanog expression. In a SCID mouse xenograft model, SAHA significantly enhanced the anti-tumor effects of cisplatin treatment with no added systemic toxicity. Furthermore, SAHA and cisplatin combination treatment significantly decreased tumor metastasis and nanog expression, in vivo. Taken together, our results suggest that targeting HDACs with SAHA could be an effective treatment strategy for the treatment of HNSCC patients.

Telomere shortening in mucosa surrounding the tumor: Biosensor of field cancerization and prognostic marker of mucosal failure in head and neck squamous cell carcinoma

The aim of the present study was to investigate the pattern of telomere length and telomerase expression in cancer tissues and the surrounding mucosa (SM), as markers of field cancerization and clinical outcome in patients successfully treated for with head and neck squamous cell carcinoma (HNSCC). This investigation was a prospective cohort study. Telomere length and levels of telomerase reverse transcriptase (TERT) transcripts were quantified by real-time PCR in cancer tissues and SM from 139 and 90 patients with HNSCC, respectively. No correlation was found between age and telomere length in SM. Patients with short telomeres in SM had a higher risk of mucosal failure (adjusted HR=4.29). Patients with high TERT levels in cancer tissues had a higher risk of regional failure (HR=2.88), distant failure (HR=7.27), worse disease-specific survival (HR for related death=2.62) but not mucosal failure. High-risk patients having both short telomeres in SM and high levels of TERT in cancer showed a significantly lower overall survival (HR=2.46). Overall these findings suggest that telomere shortening in SM is a marker of field cancerization and may precede reactivation of TERT. Short telomeres in SM are strongly prognostic of mucosal failure, whereas TERT levels in cancer tissues increase with the aggressiveness of the disease and are prognostic of tumor spread.

Preoperative radiation and free flap outcomes for head and neck reconstruction: a systematic review and meta‐analysis

There is a general consensus among reconstructive surgeons that preoperative radiotherapy is associated with a higher risk of flap failure and complications in head and neck surgery. Opinion is also divided regarding the effects of radiation dose on free flap outcomes and timing of preoperative radiation to minimize adverse outcomes. Our meta-analysis will attempt to address these issues. A systematic review of the literature was conducted in concordance to PRISMA protocol. Data were combined using STATA 12 and Open Meta-Analyst software programmes. Twenty-four studies were included comparing 2842 flaps performed in irradiated fields and 3491 flaps performed in non-irradiated fields. Meta-analysis yielded statistically significant risk ratios for flap failure (RR 1.48, P = 0.004), complications (RR 1.84, P < 0.001), reoperation (RR 2.06, P < 0.001) and fistula (RR 2.05, P < 0.001). Mean radiation dose demonstrated a trend towards increased risk of flap failure, but this was not statistically significant. On subgroup analysis, flaps with >60 Gy radiation had a non-statistically significant higher risk of flap failure (RR 1.61, P = 0.145). Preoperative radiation is associated with a statistically significant increased risk of flap complications, failure and fistula. Preoperative radiation in excess of 60 Gy after radiotherapy represents a potential risk factor for increased flap loss and should be avoided where possible.