Organ Preservation Protocol Research Articles

Upfront Neck Dissection in Organ Preservation Protocol in Head-Neck SCC : Can it be a Game Changer?

The major prognostic factor in head-neck squamous cell carcinoma is the status of lymph nodes. Though there are studies addressing the role of neck dissection in organ preservation protocol, a lacuna still exists as far as the question of upfront neck dissection arises. Despite the potential benefits of upfront neck dissection; the benefits have not been well researched and thus its place in management of head-neck cancers undergoing organ preservation protocol is still questionable. We conducted an observational study in 22 patients with T1 - 2N2 - 3a biopsy proven squamous cell carcinoma of hypopharynx, oropharynx and laryngopharynx which were eligible for organ preservation protocol for their primary site. The primary outcome was to calculate their overall survival rate at 5 years. Overall 5 year survival rate was 68.12%, 5-year Disease free survival rate was 77.2%. The time to start for the primary site, after neck dissection however had a significant effect on overall survival. Those who had a delay of 21 days or less had 80.1% survival at 5 years compared to those who started at 30 days (61.3%) and drastically reduced in those who started at 39 days (20.4%). Log-rank test for the effect of nodal status showed a significant difference in terms of 5 year survival between the groups(p = .027). The 5 year survival rates for N2A, N3A and N2B nodal status were 88.8%, 50% ,and 54.5% ,respectively. We strongly favour upfront neck dissections in a subset of head-neck squamous cell carcinoma cases with T1 - 2N2 - 3a eligible for organ preservation regimen.

Long-Term Survival and Functional Recovery of Cryopreserved Vascularized Groin Flap and Below-the-Knee Rat Limb Transplants.

Effective cryopreservation of large tissues, limbs, and organs has the potential to revolutionize medical post-trauma reconstruction options and organ preservation and transplantation procedures. To date, vitrification and directional freezing are the only viable methods for long-term organ or tissue preservation, but are of limited clinical relevance. This work aimed to develop a vitrification-based approach that will enable the long-term survival and functional recovery of large tissues and limbs following transplantation. The presented novel two-stage cooling process involves rapid specimen cooling to subzero temperatures, followed by gradual cooling to the vitrification solution (VS) and tissue glass transition temperature. Flap cooling and storage were only feasible at temperatures equal to or slightly lower than the VS Tg (i.e., -135°C). Vascularized rat groin flaps and below-the-knee (BTK) hind limb transplants cryopreserved using this approach exhibited long-term survival (>30 days) following transplantation to rats. BTK-limb recovery included hair regrowth, normal peripheral blood flow, and normal skin, fat, and muscle histology. Above all, BTK limbs were reinnervated, enabling rats to sense pain in the cryopreserved limb. These findings provide a strong foundation for the development of a long-term large-tissue, limb and organ preservation protocol for clinical use.

Induction chemotherapy-based organ-preservation protocol improve the function preservation compared with immediate total laryngectomy for locally advanced hypopharyngeal cancer-Results of a matched-pair analysis.

We performed a paired analysis to compare the therapeutic effect between the induction chemotherapy-based organ-preservation approach and immediate total laryngectomy in hypopharyngeal squamous cell carcinoma patients requiring total laryngectomy. 351 patients who were treated with organ-preservation approach were compared with 110 patients who were treated with total laryngectomy. The main measures and outcomes were progression-free survival (PFS), overall survival (OS), and larynx function preservation survival (LFPS). No statistical difference was observed for 3-, 5-, and 10-year PFS and OS in two groups. In the organ-preservation group, the 3-, 5-, and 10-year LFPS was 30.7%, 23.3%, and 16.6%, respectively. The LFPS of Stage III > Stage IV, N0 > N1 > N2 > N3, T2 > T3 > T4, CR > PR > SD > PD patients (all p values <0.05). Survival outcomes did not significantly differ between the two groups. The organ-preservation approach allowed more than 70% of the survivors to retain their larynx function.

Key clinical trials in rectal cancer shaping the current treatment paradigms: reference guide for radiologists.

Total neoadjuvant therapy (TNT), which includes chemotherapy and radiation prior to surgical resection, has been recently accepted as the new standard of care for patients with locally advanced low and mid rectal cancers. Multiple clinical trials have evaluated this approach in the last several decades and demonstrated improvement in, local control and reduced risk of recurrence. In addition, in the course of these investigations, it has been shown that between a third and a half of patients experience a clinical complete response (cCR) after being treated with the TNT approach, leading to the development of new organ preservation protocol, now known as watch-and-wait (W&W). On this protocol, cCR patients are not referred for surgery after total neoadjuvant treatment. Instead, they remain on close surveillance and, thus, avoid potential complications associated with surgical resection. Multiple clinical trials are ongoing, investigating the long-term outcomes of these new approaches and the development of less toxic and more effective TNT regimens for LARC. Improvements in technology and rectal MRI protocols position radiologists as vital members of multidisciplinary rectal cancer management teams. Rectal MRI has become a critical tool for rectal cancer initial staging, treatment response assessment, and surveillance on W&W protocols. In this review, we summarize the findings of the pivotal clinical trials that contributed to establishing the current treatment paradigms in locally advanced rectal cancer (LARC) management, with the intention of helping radiologists play more effective roles in their multidisciplinary teams.

Non-surgical organ preservation in laryngeal and hypopharyngeal cancers: an audit from the clinic.

There is increasing concern regarding efficacy of organ preservation protocol in laryngeal and hypopharyngeal cancers. This study retrospectively assessed disease-related and functional outcomes of 191 patients with non-metastatic laryngeal or hypopharyngeal squamous cell carcinoma treated with curative intent (radiotherapy with or without chemotherapy). Seventy-six patients (39.8 per cent) had a primary cancer in the larynx, and 115 patients (60.2 per cent) had a primary cancer in the hypopharynx. The median follow up was 39 months. The 3-year time to progression, overall survival, local control and laryngectomy free survival was 56.2 per cent, 76.3 per cent, 73.2 per cent and 67.2 per cent, respectively. At the time of analysis, 83 patients (43.5 per cent) were alive and disease free at their last follow up and did not require tube feeding or tracheostomy. The laryngo-oesophageal dysfunction-free survival was 61 per cent at 3 years. Organ conservation protocols remain the standard of treatment in appropriately selected patients with laryngeal and hypopharyngeal cancers.

Role of elective neck dissection with salvage laryngectomy

BackgroundElective neck dissection with salvage laryngectomy was associated with decreased quality of life, increased operative time, and increased incidence of complications; some surgeons prefer wait-and-see observation policy. However, lymph nodes recurrence after salvage total laryngectomy during follow-up period carry very poor quality of life and very poor survival rate.The aim of this study is to investigate the risk of nodal metastases in patients undergoing salvage laryngectomy and to search for predictors of occult metastases in this group of patients. Our study included 30 patients presented with recurrent laryngeal cancer after failure of organ preservation protocol. All selected patients were without detected lymph nodes both clinically and radiologically, classified as N0 according to The TNM classification.All patients were candidate for salvage total laryngectomy and had elective neck dissection performed during surgery to detect the possible occult cervical lymph node metastasis.ResultsThe positive nodal metastasis incidence was 14% in glottic, 29% in supraglottic, and 57% in trans-glottic tumors of all positive patients. The previously indicated results showed statistically significantly increased incidence of positive LN in the supraglottic tumor site and increased incidence of negative LN in the glottic site.Regarding the recurrence T stage in our study, lymph nodes were negative for metastasis in one patient with rT1 representing 4%, 6 patients with rT2 representing 26%, and for rT3 and rT4 were 65% and 4%, respectively. The nodal metastasis was positive in 3 patients with rT3 representing 43% and 4 patients with rT4 representing 57%. No patients with rT1 or rT2 showed nodal metastasis.ConclusionsOur findings demonstrated that patients with advanced local disease at recurrence undergoing salvage total laryngectomy may benefit from an elective neck dissection.

Correlation between PET-CT and ct in the staging after the treatment of head and neck squamous cell carcinoma

ObjectiveThe aim of this study is to find out if a single imaging test is enough to follow-up on an oncological post-treatment patient. In such a case, we would know which was more valuable after comparing the two, by CT or PET-CT. MethodsBetween January 2012 and July 2018, we collected data from all patients with previous medical history who were treated with a head and neck squamous cell carcinoma in our hospital, through surgery or by using an organ preservation protocol which we had done. Patients were required to have a CT and a PET-CT performed in a maximum period of 30 days between techniques. We compared the post post-treatment stage given to each case by using only the physical examination (only the CT and the PET-CT), with the ones given by the Tumor Board. After treatment, we analysed the similarity through Cramer’s V statistic test. ResultsWe performed a comparative analysis, obtaining a correlation of 0.426 between the stages given by the Tumor Board and the one assigned based on physical examination, without imaging techniques. By only using the computed tomography as an imaging method the correlation was 0.565, whereas with only the use of positron emission computed technology, it was estimated at 0.858. When we compared the statistical association between stages using exclusively one of the two imaging techniques, the correlation was 0.451. ConclusionIndependent of the modality, we have demonstrated that in patients who have received previous treatment, there was a higher correlation in the stages with respect to the diagnostic method conducted by the Tumor Board using PET-CT as the sole image. Level of evidenceLevel 1.

P-7 Surgical versus Organ preservation protocol for stage T3/T4 laryngeal and hypopharyngeal cancer

P-7 Surgical versus Organ preservation protocol for stage T3/T4 laryngeal and hypopharyngeal cancer

Evolution of Nutritional Status in Patients with Advanced Head and Neck Cancer Undergoing Surgical Treatment or Organ Preservation Protocol

We sought to evaluate the evolution of the nutritional status of patients with advanced cancer of the upper aerodigestive tract undergoing surgical treatment (SURG) or organ preservation protocol (OP). Evaluations were conducted at the beginning and end of treatment, including weight, body composition and Patient-Generated Subjective Global Assessment (PG-SGA). Each group was comprised of 29 patients. Initially, malnutrition rates were 65.5% and 51.7% in the SURG and OP groups, respectively. At the end, the values went to 55.1% in SURG and 79.3% in OP. In the OP, there was a reduction in weight (P = 0.001), fat mass (P = 0.006), fat free mass (P = 0.002), and muscle mass (P = 0.005) and an increase in scores of the PG-SGA (P = 0.008). The same was not observed in SURG, except for the weight decrease (P = 0.025). Malnutrition was prevalent in both treatment groups and patients in OP were at greater risk of nutritional decline.

Matched-Pair Analysis of Survival in the Patients with Advanced Laryngeal and Hypopharyngeal Squamous Cell Carcinoma Treated with Induction Chemotherapy Plus Chemo-Radiation or Total Laryngectomy.

Simple SummaryThere are no randomized studies comparing organ-preservation protocols with chemo-selection to the classical total laryngectomy plus (chemo)radiotherapy. Thus, we performed a matched-pair analysis to compare these two treatments with respect to locoregional control, disease-specific survival (DSS), and overall survival (OS) in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx. The results did not show differences between the two treatments for patients with T3/T4a larynx and T2–T4a hypopharynx cancer with respect to OS and DSS, locoregional control, and metastasis-free survival.Background: We performed a comparative analysis between an organ-preservation protocol and surgery followed by radiotherapy in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx; Methods: 60 previously untreated patients who were treated with induction chemotherapy followed by chemoradiotherapy in responders were compared with a control group of 60 patients treated with up-front surgery. Both groups were statistically comparable, according to the subsite, TNM (tumor-node-metastasis) stage, age, and sex; Results: Mean age was 58 years and 92% were male. No significant statistical difference was observed for overall survival (OS) (HR 0.75; 95% CI 0.48–1.18; P = 0.22) and disease-specific survival (DSS) (HR 0.98; 95% CI 0.52–1.83, P = 0.96). Also, there was no significant difference for recurrence-free survival (HR 0.931; 95% CI 0.57–1.71; P = 0.81), metastases-free survival (HR 2.23; 95% CI 0.67–7.41; P = 0.19), and the appearance of second primary tumors (HR 1.22; 95% CI 0.51–2.88; P = 0.64); Conclusions: The results of the organ-preservation approach did not appear inferior to those of surgery plus (chemo)radiotherapy for patients with T3/T4a larynx and T2–T4a hypopharynx cancer with respect to OS and DSS, locoregional control and metastases-free survival.

Results of pretreatment swallowing evaluation in patients with stage III/IV laryngeal and hypopharyngeal carcinoma.

Laryngeal and hypopharyngeal carcinoma are among the common head and neck cancers causing considerable swallowing dysfunction. The functional status of the organ (larynx) is an important point of contention while considering the patients for organ preservation protocol. The aim of this retrospective study was to assess the swallowing status in stage III/IV laryngeal and hypopharyngeal carcinoma and its influence on treatment decision. We evaluated all treatment naïve patients who were referred to the swallowing clinic in 2017 (Jan-Dec) for assessment of swallowing prior to treatment initiation. One hundred patients satisfied the eligibility criteria and were included in the study. The site and stage of laryngeal and hypopharyngeal cancer cases were almost equal in number. Their median age was 58years. Fiberoptic endoscopic evaluation of swallowing (FEES) was done in all patients. 30% of the patients only had swallowing difficulties. Only advanced T-stage (p = 0.04) had an influence on the pretreatment swallowing status. Thirty-seven patients required nasogastric tube (NGT) for feeding. By 2month post-treatment completion, most patients on NGT could resume oral feeding. Pretreatment swallowing assessment alone did not significantly seem to influence our decisions for organ preservation treatment. However, patients with aspiration could be identified and managed appropriately. Most patients on NGT could resume oral feeds post-treatment completion.

Abstract A42: Total laryngopharyngoesophagectomy with gastric transposition for hypopharyngeal cancer: A tertiary care center experience

Abstract Introduction: With the emergence of organ preservation protocol in head and neck cancer, management of hypopharyngeal carcinoma is generally by nonsurgical approach; however, a significant number of hypopharyngeal cancer patients present in advanced stage and exhibit poor prognosis. For such cases, thorough aggressive surgical excision of laryngopharyngoesophageal complex with appropriate reconstruction might be a viable option. Objective: To evaluate quality-of-life measures and survival outcomes in hypopharyngeal carcinoma cases undergoing above-mentioned procedure at a tertiary health care center. Methodology: A retrospective study on patients with hypopharyngeal carcinoma undergoing above-mentioned procedure was done in our tertiary care institute between September 2016 to October 2018. Results: A total of 12 patients were operated during the study period; however, 3 patients were excluded due to inadequate data. In our study, mean age of presentation was 51.3 years and majority were men (n=8). Most of the patients at the time of presentation were stage IVA or more. Postcricoid was most common subsite, followed by pyriform fossa. 4 out of 12 were operated after failed chemoradiation. Perioperative morbidity primarily in terms of complications and duration of hospital stay and quality-of-life measures consisting mainly of swallowing score were analyzed, which suggested that this procedure is tolerable and produces a reliable outcome. Conclusion: Total laryngopharyngoesophagectomy with gastric transposition is a feasible and efficacious treatment option with reasonable quality of life in carcinoma hypopharynx patients, especially after failed chemoradiation. Citation Format: Prerit Rao, K. Devaraja, Kailesh Pujary, Dipak Ranjan Nayak, R. Balakrishnan. Total laryngopharyngoesophagectomy with gastric transposition for hypopharyngeal cancer: A tertiary care center experience [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr A42.

1114PD - High immunoscore is associated with good response to neo-adjuvant chemotherapy and prolonged survival in advanced head and neck cancer patients

BackgroundThe presence of high levels of tumor immune infiltrate has been recognized to be associated with better prognosis in Head and Neck cancer (H&N). The consensus Immunoscore quantifies the densities of CD3 and CD8 in the center of the tumour (CT) and the invasive margin (IM) and stratifies patients into 3 Immunoscore categories (Low, Intermediate and High).Table: 1115PDTable: 1115PDCutpointSensitivitySpecificityN (prevalence)ORR, %Odds Ratio (CI)PFS HR (CI)OS HR (CI)TPS ≥50%0.470.7765 (0.27)26.23.83 (1.31, 11.15)0.59 (0.40, 0.87)0.54 (0.36, 0.82)TPS ≥20%0.560.6494 (0.39)21.31.84 (0.83, 4.11)0.72 (0.52, 0.99)0.66 (0.47, 0.93)TPS ≥1%0.640.44140 (0.57)16.41.56 (0.79, 3.10)0.95 (0.74, 1.22)0.75 (0.57, 0.97)CPS ≥500.500.7864 (0.26)28.14.70 (1.62, 13.59)0.60 (0.41, 0.89)0.60 (0.40, 0.91)CPS ≥200.580.6496 (0.39)21.92.42 (1.10, 5.33)0.75 (0.55, 1.01)0.63 (0.46, 0.86)CPS ≥10.940.23195 (0.80)17.41.85 (1.01, 3.37)0.89 (0.72, 1.11)0.72 (0.58, 0.91)All1.000.00244 (1.00)14.81.43 (0.83, 2.46)0.94 (0.77, 1.14)0.79 (0.65, 0.97)CPS, combined positive score; HR, hazard ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; SOC, standard of care; TPS, tumor proportion score.Sensitivity, specificity, N (prevalence), and ORR are for the pembrolizumab arm. Odds ratio, PFS HR, and OS HR compare pembrolizumab and SOC. MethodsThis retrospective ongoing study evaluated the Immunoscore in 110 patients with advanced laryngeal (n=57) or hypopharyngeal (n=53) cancers who received neo-adjuvant chemotherapy in the setting of an organ preservation protocol. Good responders (tumor reduction > 50%) were subsequently treated by radiation/chemoradiation, whereas non-responders were subjected to surgery followed by post-operative radiation/chemoradiation. Pre-treatment tumor samples were immune-stained for T-cell (CD3, CD8) markers and quantitative analysis of the immune cells was carried out in different tumor locations using a computer-assisted image analysis. Results60% of patients were good responders. Densities of T cell infiltration were significantly higher for Hypopharyngeal cancer patients compared to those with laryngeal cancer. ( P<0.001) Analysis of the entire cohort showed that good-responders had a higher Immunoscore than non-responders (69% vs. 39%% respectively, Odd Ratio = 2.7303CI 95%[0.8497-9.24], P=0.069). Immunoscore Low, Intermediate and High represented respectively 16.5%, 45.6% and 37.9% of the cohort. High Immunoscore patients were at low risk of relapse, with 5-year Time to Recurrence rates of 71.4 (CI 53.9−94.6) as compared to 54.6CI 95% (40.4−73.9) and 31.4CI 95% (13.3−74.1) in intermediate and low Immunoscore patients respectively (HR=1.9CI 95% (1.2−3.0), P<0.02). Similar results were found in Larynx and Hypopharynx separately. Regardless of treatment type and tumor location, a high Immunoscore was associated with better progression-free survival and overall survival. ConclusionsThe results of this ongoing study show a significant prognostic and potentially predictive role of Immunoscore in H&N cancer patients with important therapeutic implications. Legal entity responsible for the studyHaitham Mirghani. FundingHalioDx. DisclosureH. Mirghani: Advisory / Consultancy: MSD vaccin; Travel / Accommodation / Expenses: BMS. B. Mlecnik: Licensing / Royalties: HalioDx. F. Hermitte: Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: HalioDx. C. Even: Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy: Innate Pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca. J. Galon: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: HalioDx; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Merck Serono; Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): Sanofi; Honoraria (self): Gilead; Advisory / Consultancy, Research grant / Funding (institution): IOBiotech; Advisory / Consultancy: Illumina; Advisory / Consultancy: Northwest Biotherapeutics; Advisory / Consultancy: Actelion; Advisory / Consultancy: Amgen; Research grant / Funding (institution): Perkin-Helmer; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Imcheck; Licensing / Royalties: Inserm. All other authors have declared no conflicts of interest.

Study of Dysphagia in Patients with Advanced Oropharyngeal Cancer Subjected to an Organ Preservation Protocol Based on Concomitant Radiotherapy and Chemotherapy

Introduction:Organ preservation protocol (based on chemo-radiotherapy) for oropharyngeal tumors include dysphagia as a possible sequel leading to function impairment and changes in patient’s quality of life.Objectives:The aim of this study is to assess dysphagia severity after treatment in advanced oropharyngeal cancer patients treated with concurrent chemo-radiation.Methods:This prospective cross-sectional study included 64 participants who had been disease free for at least six months after primary treatment. Dysphagia severity was assessed by fibre-optic endoscopic evaluation of swallowing (FEES) and the Dysphagia Outcome and Severity Scale (DOSS); the occurrence of penetration/aspiration during swallowing was also investigated. All participants also completed the M. D. Anderson Dysphagia Inventory (MDADI). The correlation of FEES results with clinical-demographic variables and MDADI scores was assessed. Descriptive analysis was performed, and qualitative variables were compared using either the chi-square or Fisher’s exact test.Results:FEES revealed silent aspiration in 18.8% of the patients. Approximately 6.3% of the patients exhibited severe dysphagia (scores 1-2 in DOSS). Dysphagia severity was significantly associated with the MDADI physical domain scores. The participants with scores 5-7 in DOSS (no or mild dysphagia) exhibited less limitations in the MDADI physical domain (p=0.015).Conclusions:Silent aspiration was detected in one of every five patients treated with concurrent chemo-radiotherapy; almost half of the patients exhibit at least moderate dysphagia. Assessment of the participant’s quality of life via the MDADI revealed an association between the physical domain scores and dysphagia severity.

Computed tomography evaluation after induction chemotherapy for T3 laryngeal cancer: Does response correlate with vocal cord mobility?

ObjectivesAfter induction chemotherapy (IC) for laryngeal cancer, Computed Tomography (CT) is used to assess tumor response but lacks rationalized methods for measurement of this response. In T3 laryngeal cancer, remobilization of an initially fixed vocal cord (VC) is a major sign of tumor response. We compared the performances of RECIST1.1, WHO and volumetric methods of evaluating response with laryngeal remobilization to determine if these measurements could objectively assess tumor response. Material and MethodsThis monocentric retrospective cohort study included patients treated with T3 laryngeal cancer with initial VC fixation treated with an organ preservation protocol with IC between 1999 and 2012. Tumors were measured with CT using RECIST1.1, WHO and volumetric methods by two radiologists blinded to VC remobilization (VCR), before and after induction chemotherapy and VC mobility was clinically assessed. Radiologic tumor shrinkage was compared to VCR. AUCs of ROC curves were compared. Inter-reader reliability, sensitivity and specificity of optimal cutoffs were determined. ResultsSeven females and thirty-six males with a mean age of 59 years were included. AUCs were 0.759, [95%CI 0.614; 0.904] for RECIST1.1, 0.763, [95%CI 0.617; 0.909] for WHO and 0.752, [95%CI 0.608; 0.896] for volumetric evaluations with no significant difference among the three techniques. Inter-reader reader reliabilities were good (RECIST1.1) to excellent (WHO and volumetric methods). ConclusionRECIST1.1, WHO and volumetric measures match with VCR after IC in patient with T3 laryngeal cancer. WHO criteria combine accuracy, reproducibility and practical use; they may be best adapted for response assessment and protocol design.

Organ preservation vs primary surgery in the management of T3 laryngeal and hypopharyngeal cancers.

The main objective is to compare the oncologic outcomes of patients with T3 laryngeal cancers who underwent total laryngectomy or organ preservation protocol (OPP) as the initial plan of management. This is a retrospective study on 120 patients treated for T3 laryngeal and hypopharyngeal cancers. Patients with functional larynx underwent OPP and dysfunctional larynx underwent upfront laryngectomy. Median follow-up of the patients was 4.6years. There was a significant difference in 3year disease-free survival (DFS) between upfront laryngectomy and OPP (73.2 vs. 55.7%; P = 0.028) group but not in 3year overall survival (73.2 vs. 68.7%, P = 0.8). The rate laryngeal preservation was 65% in CCRT and 44% in only radiotherapy group. At 3years, the laryngectomy-free survival was 57.2% and the laryngo-esophageal dysfunction-free survival (LEDS) was 53.0%. T3 laryngeal cancers treated with upfront laryngectomy have an improved DFS when compared to those treated with non-surgical modalities. Primary surgery should be offered as an option for selected patients especially when CCRT is not feasible.

Efficacy of the Myofascial Pectoralis Major Flap in the Reduction of Salivary Fistulas After Salvage Total Laryngectomy

IntroductionPharyngocutaneous fistula is the most frequent complication after total laryngectomy. Its incidence varies between 9%–25% in post primary total laryngectomy patients, to 14%–57% in salvage laryngectomy post radiotherapy or post chemotherapy+radiotherapy. The pectoralis major myofascial flap (PMMF) is postulated as a useful tool to decrease the incidence of this complication. Materials and methodRetrospective analysis of a group of patients treated by salvage laryngectomy, associated or not with pharyngeal closure reinforcement with PMMF. ResultsTwenty patients were included, 18 males (90%) and 2 females (10%), in 10 of whom the PMMF was used. The average age was 66.65 years. Seventeen (85%) had a laryngeal tumour and 3 (15%) had a hypopharyngeal tumour. Eight (80%) patients in the non-PMMF group had postoperative fistula, whereas only 2 (20%) patients in the PMMF group had a fistula during the postoperative period (P=.005). The mean time for fistula closure was significantly shorter in the cases where PMMF flap was used (16±11 days vs. 76.8±67 days, P=.001), as was hospital stay (19.6±18 days vs. 83.9±77 days, P=.001). ConclusionThe use of PMMF in our series is associated with a lower rate of post salvage laryngectomy fistulas in patients treated primarily by organ preservation protocol for laryngeal/hypopharyngeal cancer. In turn, it promotes local healing by decreasing the mean duration of fistula closure and the mean hospital stay.

Abstract A30: Depicting clinically relevant molecular alterations in oropharynx squamous cell carcinoma samples treated with an organ preservation protocol

Abstract Introduction: Head and neck cancers are among the most common human malignancies in the world, with high rates of morbidity and mortality. These tumors are mostly caused by heavy tobacco smoking; however, high-risk human papillomavirus (HR-HPV) infection has been increasingly associated with tumors in the oropharynx. Oropharynx squamous cell carcinomas (OPSCC) associated with HR-HPV infection represent a distinct clinical and epidemiologic entity, with differences in clinical presentation and treatment outcome reflecting distinct genetic and biologic profiles. Initial treatment decisions are critical to improve patient survival; therefore, considering that multimodality therapy is often toxic, treatment choice should balance tolerability, function preservation, and global response to therapy. Molecular markers may be beneficial in a better classification of patients, thus aiding in a more consistent tailoring of patient treatment and follow-up. Objective: The aim of this study was to identify specific clinical and molecular profiles that classify subgroups of OPSCC patients according to their outcome. Materials and Methods: Thirty OPSCC samples from patients treated with a chemoradiation-based organ-preservation protocol were included in this study. P16 protein expression was used as a surrogate marker for HR-HPV. The methylation status of 5 genes was evaluated by quantitative methylation-specific PCR (qMSP), and next-generation sequencing of a 15-gene panel was performed using the Ion Torrent PGM platform. Results: The majority of patients (93.3%) were male, tobacco users (85.2%), presented with advanced disease (90%), and 36.7% were HR-HPV positive. Specific gene-promoter hypermethylation was observed in 32.1-50% of the OPSCC evaluated and, as expected, CCNA1 methylation was associated with HPV(+ve) cases (p=0.035). Eighteen patients (58.1%) had at least 1 gene mutated: 87.5% of HPV(-ve) and 57.1% of HPV(+ve) cases. Interestingly, 60% of smokers HPV(+ve) cases were wild-type for TP53 variants (p=0.003). The absence of deleterious variants in several genes (EZH2, FAT1, FBWX7, HRAS, IRF6, PIK3CA, and PTEN) was significantly associated with a complete response of the primary tumor site to the organ-preservation treatment protocol (p&amp;lt;0.004). Conclusions: Even though all samples analyzed were of the oropharynx, several differences regarding molecular and clinical characteristics were identified. An association between molecular markers and the profile of therapy response can be useful in decision-making of the initial treatment and improve patient survival. More cases are being evaluated in order to assess whether the differences identified are able to significantly classify these patients into molecular subgroups associated with different outcomes and help in more thorough patient management. Citation Format: Ana Carolina de Carvalho, Matias Eliseo Melendez, Cristovam Scapulatempo Neto, Gabriela Carvalho Fernandes, Lidia Maria Rebolho Batista Arantes, Bruna Pereira Sorroche, Gisele Caravina de Almeida, Rui Manuel Reis, Sandra Perdomo, André Lopes Carvalho. Depicting clinically relevant molecular alterations in oropharynx squamous cell carcinoma samples treated with an organ preservation protocol [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A30.

Abstract A34: SNPs as predictors in the tailoring of treatment for HNSCC patients undergoing organ preservation protocols

Abstract Background: The treatment of early-stage head and neck squamous cell carcinoma (HNSCC) tumors is conducted through a multimodality approach including surgery, radiation, and chemotherapy, with curative rates of approximately 80-90%. However, only 30-50% of patients with locally advanced disease survive more than five years, despite the advances in surgical techniques and the recognized benefits of chemoradiation. In this scenario, improvement in patients' survival requires both early detection as well as the possibility of predicting, at the moment of diagnosis, which patients will benefit from a specific treatment. Tailoring the treatment is of great importance and may help in the management of treatment planning and follow-up, improving survival rates. Objectives: The aim of the present study was to evaluate SNPs in genes involved in induction chemotherapy with cisplatin and paclitaxel, which are able to predict the response to an organ-preservation protocol based on chemoradiation. Materials and Methods: For this purpose, we assessed the profile of 3.223 SNPs of 59 HNSCC patients with locally advanced and unresectable tumors undergoing treatment using the IonTorrent plataform. Results: From 3,223 SPNs, only 323 were present in the study population and 21 SNPs showed a significant association with response to induction chemotherapy and/or concomitance. Regarding induction chemotherapy response, thirteen polymorphisms were statistically associated. The presence of SNPs rs776746 (CYP3A5 gene) (p=0.03), rs1883322 (PPARD gene) (p=0.03), rs10932374 (ERBB4 gene) (p=0.03), and rs2230806 (ABCA1 gene) (p=0.04) was associated with a favorable treatment response, whereas the remaining polymorphisms with statistical significance were associated with a lack of therapeutic response. It is interesting to note that the presence of three polymorphisms (rs10509681 (p=0.001), rs1058930 (p=0.03), and rs11572080 (p≤0.001)) in the CYP2C8 gene was associated with treatment resistance, showing the importance of these polymorphisms in the process of chemotherapy resistance. Similarly, polymorphisms rs12415607 (p=0.01), rs4353229 (p=0.02), and rs2227310 (p=0.02) in the CASP7 gene were associated with resistance to chemotherapy. Conclusion: The results of this study suggest that the evaluation of SNPs could be an important tool for treatment planning and a prognosis predictor for HNSCC patients undergoing organ preservation protocols. Citation Format: Lidia Rebolho Batista M. R. B., Pamela Angelique Kuhlmann, Matias Eliseo Melendez, Ana Carolina Laus, Ana Carolina de Carvalho, Pedro Rafael Martins De Marchi, Adriane Feijó Evangelista, Viana de Souza Luciano, Carvalho Lopes André. SNPs as predictors in the tailoring of treatment for HNSCC patients undergoing organ preservation protocols [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A34.

Efectividad del colgajo de músculo pectoral mayor miofascial en la reducción de fístulas salivares tras laringectomía total de rescate

IntroductionPharyngocutaneous fistula is the most frequent complication after total laryngectomy. Its incidence varies between 9%-25% in post primary total laryngectomy patients, to 14%-57% in salvage laryngectomy post radiotherapy or post chemotherapy + radiotherapy. The pectoralis major myofascial flap (PMMF)is postulated as a useful tool to decrease the incidence of this complication. Materials and methodRetrospective analysis of a group of patients treated by salvage laryngectomy, associated or not with pharyngeal closure reinforcement with PMMF. ResultsTwenty patients were included, 18 males (90%) and 2 females (10%), in 10 of whom the PMMF was used. The average age was 66.65 years. Seventeen (85%) had a laryngeal tumour and 3 (15%) had a hypopharyngeal tumour. Eight (80%) patients in the non-PMMF group had postoperative fistula, whereas only 2 (20%) patients in the PMMF group had a fistula during the postoperative period (P=.005). The mean time for fistula closure was significantly shorter in the cases where PMMF flap was used (16±11 days vs. 76.8±67 days, P=.001), as was hospital stay (19. 6±18 days vs. 83.9±77 days, P=.001). ConclusionThe use of PMMF in our series is associated with a lower rate of post salvage laryngectomy fistulas in patients treated primarily by organ preservation protocol for laryngeal/hypopharyngeal cancer. In turn, it promotes local healing by decreasing the mean duration of fistula closure and the mean hospital stay.