Protective effect of height on long-term survival of resectable lung cancer: a new feature of the lung cancer paradox.

INTRODUCTION: Unlike most malignancies, higher body mass index (BMI) is associated with a reduced risk of lung cancer and improved prognosis after surgery. However, it remains controversial whether height, one of determinants of BMI, is associated with survival independently of BMI and other confounders. METHODS: We extracted data on all consecutive patients with resectable non-small cell lung cancer included in Epithor, the French Society of Thoracic and Cardiovascular Surgery database, over a 16-year period. Height was analysed as a continuous variable, and then categorised into four or three categories, according to sex-specific quantiles. Cox proportional hazards regression was used to estimate the association of height with survival, adjusted for age, tobacco consumption, forced expiratory volume in one second (FEV1), WHO performance status (WHO PS), American Society of Anesthesiologists (ASA) score, extent of resection, histological type, stage of disease and centre as a random effect, as well as BMI in a further analysis. RESULTS: The study included 61 379 patients. Higher height was significantly associated with better long-term survival after adjustment for other variables (adjusted HR 0.97 per 10 cm higher height, 95% CI 0.95 to 0.99); additional adjustment for BMI resulted in an identical HR. The prognostic impact of height was further confirmed by stratifying by age, ASA class, WHO PS and histological type. When stratifying by BMI class, there was no evidence of a differential association (p=0.93). When stratifying by stage of disease, the prognostic significance of height was maintained for all stages except IIIB-IV. CONCLUSIONS: Our study shows that height is an independent prognostic factor of resectable lung cancer.

Survival outcomes following urgent lung transplantation in France and the USA.

INTRODUCTION: Lung graft allocation can be based on a score (Lung Allocation Score) as in the USA or sequential proposals combined with a discrete priority model as in France. We aimed to analyse the impact of allocation policy on the outcome of urgent lung transplantation (LT). METHODS: US United Network for Organ Sharing (UNOS) and French Cristal databases were retrospectively reviewed to analyse LT performed between 2007 and 2017. We analysed the mortality risk of urgent LT by fitting Cox models and adjusted Restricted Mean Survival Time. We then compared the outcome after urgent LT in the UNOS and Cristal groups using a propensity score matching. RESULTS: After exclusion of patients with chronic obstructive pulmonary disease/emphysema and redo LT, 3775 and 12 561 patients underwent urgent LT and non-urgent LT in the USA while 600 and 2071 patients underwent urgent LT and non-urgent LT in France. In univariate analysis, urgent LT was associated with an HR for death of 1.24 (95% CI 1.05 to 1.48) in the Cristal group and 1.12 (95% CI 1.05 to 1.19) in the UNOS group. In multivariate analysis, the effect of urgent LT was attenuated and no longer statistically significant in the Cristal database (HR 1.1 (95% CI 0.91 to 1.33)) while it remained constant and statistically significant in the UNOS database (HR 1.12 (95% CI 1.05 to 1.2)). Survival comparison of urgent LT patients between the two countries was significantly different in favour of the UNOS group (1-year survival rates 84.1% (80.9%-87.3%) vs 75.4% (71.8%-79.1%) and 3-year survival rates 66.3% (61.9%-71.1%) vs 62.7% (58.5%-67.1%), respectively). CONCLUSION: Urgent LT is associated with adverse outcome in the USA and in France with a better prognosis in the US score-based system taking post-transplant survival into account. This difference between two healthcare systems is multifactorial.

Rapidly growing breast desmoid tumor with intra-thoracic involvement after reconstructive surgery for breast cancer.

Desmoid tumors are very rare soft tissue neoplasia that are slow growing and locally aggressive. They grow anywhere in the body and are rarely develop in the breast . Histopathologic examination confirms diagnosis. Recurrence rate is very high even after complete resection. We report the management of a rare case of rapidly growing breast desmoid with intra-thoracic involvement causing cardiac compression.

Use of Ultrasonography for Lung Transplant Recipients on Postoperative Care.

The authors report their findings regarding lung ultrasound profiles in a population of transplant recipients. Twenty-two patients were studied once each in multiple different ultrasound windows focusing on pleural, lung, and diaphragmatic signatures. All studies were performed in presumably otherwise healthy recipients at an outpatient follow-up visit at least 3 months after transplantation. Those with recent pulmonary infections or decline in lung function were excluded from enrollment. The majority of scans revealed otherwise normal lungs with lung sliding, but there were more abnormalities than one would expect in a healthy control group. Lung ultrasonography will likely never replace other cross-sectional imaging given its inherent visual limitations but adds another modality to interrogate the lung/pleural interface and diaphragmatic function.

Wilms tumor, pleuropulmonary blastoma, and DICER1: case report and literature review.

BACKGROUND: Pleuroblastoma (PPB) is a rare pediatric tumor which, in 30% of cases, is associated with cystic nephroma. It has been recently linked to the DICER1 mutation as part of a predisposition syndrome for various tumors. However, if DICER 1 anomalies have been reported in patients with Wilms tumor (WT), to date, no cases of PPB, WT, and DICER1 mutations have been reported in the same patient. CASE PRESENTATION: We report the case of a 3-year-old patient, initially managed for metastatic WT. During his clinical course, the diagnosis of a PPB was made after detecting the DICER1 mutation and subsequent management was therefore modified. CONCLUSION: This case highlights that in case of simultaneous discovery of a renal tumor and a pulmonary lesion in a child, the DICER 1 mutations should be looked for as these could help adapt management and schedule the surgical procedures.

Risk factors for survival and recurrence after lung metastasectomy.

BACKGROUND: Colorectal cancer (CRC) is the third most diagnosed cancer worldwide, with up to 25% of patients who will develop metastases. Pulmonary metastases (PMs) resection for CRC might improve long-term survival, but the selection criteria for patients who would benefit remain unclear. The aim of this study was to identify preoperative predictive factors in patients eligible for this surgical strategy. MATERIALS AND METHODS: We retrospectively reviewed data of patients from five thoracic surgery departments who underwent PM resection for CRC with intent to cure between 2005 and 2010. Univariate and multivariate analyses were performed to identify predictive factors influencing long-term survival and recurrence after pulmonary resection. RESULTS: Three hundred fifty-four patients were eligible. Forty-eight patients had pulmonary recurrence (13.5%). Thirty-day postoperative mortality was 0.3% (n = 1). Five- and 8-y overall survival (OS) were 64.3 ± 3.99% and 60.72 ± 4.5%, respectively. In univariate analysis, 5-y OS was significantly associated with an American Society of Anesthesiologists score of 1 (P = 0.02), a low number of PM (P = 0.001), and single wedge resection (P = 0.00001). In multivariate analysis, an American Society of Anesthesiologists score of 3 or higher (P = 0.05), two or more PMs (P = 0.034) and pneumonectomy (P = 0.021) were significant predictors of a poor outcome. In univariate analysis, 5-y cumulative recurrence was significantly associated with the absence of mediastinal lymph node dissection (P = 0.01). CONCLUSIONS: Given its high 5-y OS with low postoperative morbidity, thus allowing repeat surgical management, resection of PM could be performed. Resection of PM could improve long-term survival.

Real-world outcomes of lobectomy, segmentectomy and wedge resection for the treatment of stage c-IA lung carcinoma.

OBJECTIVES: To determine safety and survival outcomes associated with lobectomy, segmentectomy and wedge resection for early-stage lung cancer by quiring the French population-based registry EPIdemiology in THORacic surgery (EPITHOR). METHODS: Retrospective analysis of 19 452 patients with stage c IA lung carcinoma who underwent lobectomy, segmentectomy or wedge resection between 2016 and 2022 with curative-intent. Main outcome measures were 90-day mortality and 5-year overall survival estimates. Proportional hazards regression and propensity score matching were used to adjust outcomes for key patient, tumour and practice environment factors. RESULTS: The treatment distribution was 72.2% for lobectomy, 21.5% for segmentectomy and 6.3% for wedge. Unadjusted 90-day mortality rates were 1.6%, 1.2% and 1.1%, respectively (P = 0.10). Unadjusted 5-year overall survival estimates were 80%, 78% and 70%, with significant inter-group survival curves differences (P < 0.0001). Multivariable proportional hazards regression showed that wedge was associated with worse overall survival [adjusted hazard ratio (AHR), 1.23 (95% confidence interval 1.03-1.47); P = 0.021] compared with lobectomy, while no significant difference was disclosed when comparing segmentectomy to lobectomy (1.08 [0.97-1.20]; P = 0.162). The three-way propensity score analyses confirmed similar 90-day mortality rate for wedge resection and segmentectomy compared with lobectomy (hazard ratio: 0.43; 95% confidence interval 0.16-1.11; P = 0.081 and 0.99; 0.48-2.10; P = 0.998, respectively), but poorer overall survival (1.45; 1.13-1.86; P = 0.003 and 1.31; 1-1.71; P = 0.048, respectively). CONCLUSIONS: Wedge resection was associated with comparable 90-day mortality but lower overall survival when compared to lobectomy. Overall, all types of sublobar resections may not offer equivalent oncologic effectiveness in real-world settings.

Impact of surgical approach on 90-day mortality after lung resection for nonsmall cell lung cancer in high-risk operable patients.

Introduction: Non-small cell lung cancer (NSCLC) is often associated with compromised lung function. Real-world data on the impact of surgical approach in NSCLC patients with compromised lung function are still lacking. The objective of this study is to assess the potential impact of minimally invasive surgery (MIS) on 90-day post-operative mortality after anatomic lung resection in high-risk operable NSCLC patients. Methods: We conducted a retrospective multicentre study including all patients who underwent anatomic lung resection between January 2010 and October 2021 and registered in the Epithor database. High-risk patients were defined as those with a forced expiratory volume in 1 s (FEV1) or diffusing capacity of the lung for carbon monoxide (DLCO) value below 50%. Co-primary end-points were the impact of risk status on 90-day mortality and the impact of MIS on 90-day mortality in high-risk patients. Results: Of the 46 909 patients who met the inclusion criteria, 42 214 patients (90%) with both preoperative FEV1 and DLCO above 50% were included in the low-risk group, and 4695 patients (10%) with preoperative FEV1 and/or preoperative DLCO below 50% were included in the high-risk group. The 90-day mortality rate was significantly higher in the high-risk group compared to the low-risk group (280 (5.96%) versus 1301 (3.18%); p<0.0001). In high-risk patients, MIS was associated with lower 90-day mortality compared to open surgery in univariate analysis (OR=0.04 (0.02-0.05), p<0.001) and in multivariable analysis after propensity score matching (OR=0.46 (0.30-0.69), p<0.001). High-risk patients operated through MIS had a similar 90-day mortality rate compared to low-risk patients in general (3.10% versus 3.18% respectively). Conclusion: By examining the impact of surgical approaches on 90-day mortality using a nationwide database, we found that either preoperative FEV1 or DLCO below 50% is associated with higher 90-day mortality, which can be reduced by using minimally invasive surgical approaches. High-risk patients operated through MIS have a similar 90-day mortality rate as low-risk patients.

A 3D-engineered silicone stent to treat a refractory bronchopleural fistula.

A novel 3D-engineered silicone stent was successfully used to treat a refractory bronchopleural fistula of the right lower lobe in a patient with an open-window thoracostomy who complained of severe dysphonia and recurrent infections https://bit.ly/3GrKs2p.

Reaching multidisciplinary consensus on the management of non-bulky/non-infiltrative stage IIIA N2 non-small cell lung cancer.

INTRODUCTION: The optimal management of patients with non-bulky/non-infiltrative stage IIIA N2 non-small cell lung cancer (NSCLC) remains controversial. In this modified Delphi study from France, we aimed to generate agreement through multidisciplinary decision-making on the clinical management of patients with non-bulky/non-infiltrative N2 NSCLC. METHODS: An expert panel of 30 physicians from different specialities completed two Delphi rounds of a 76-item questionnaire, pertaining to: pathological confirmation of N2 disease; initial treatment approach; treatment approach in case of disease progression/stability following neoadjuvant chemotherapy; treatment approach taking into account various patient and tumour characteristics. Each questionnaire item was scored using a 9-point Likert scale. Consensus in agreement was achieved if ≥ 80 % of responses to a questionnaire item were scored between 7 and 9 and if the median value of the score to the item was ≥ 7. RESULTS: Regarding the pathologic confirmation of N2 disease, agreement (up to 100 %) was reached on endobronchial ultrasound/endoscopic ultrasound as the preferred method of initial mediastinal staging for paratracheal lymph nodes. There was also panellist agreement (up to 93 %) on the adoption as first-line treatment of surgery and (neo)adjuvant chemotherapy in patients with single-station disease, and of concurrent chemoradiotherapy followed by adjuvant immunotherapy in those with multi-station N2 disease. Panellists further agreed on the use of a non-surgical strategy, i.e., concurrent chemoradiotherapy with adjuvant immunotherapy, in patients with single-station N2 disease in case of: involvement of ≥ 2 mediastinal lymph nodes; disease progression following neoadjuvant chemotherapy; compromised cardiopulmonary function if compatible with radiotherapy; anticipated right pneumonectomy. CONCLUSIONS: This Delphi study reinforces the importance of multidisciplinary discussions leading to the best individual approach to the clinical management of patients with non-bulky/non-infiltrative N2 NSCLC, a challenging heterogeneous population.

Prognostic score and sex-specific nomograms to predict survival in resectable lung cancer: A French nationwide study from the Epithor cohort database.

Background: Prognostic assessment in patients undergoing cancer treatments is of paramount importance to plan subsequent management. In resectable lung cancer availability of an easy-to use nomogram to predict long-term outcome would be extremely useful to identify high-risk patients in the era of perioperative targeted and immune therapies. Methods: We retrieved clinical, surgical and pathological data of all consecutive patients included in Epithor, the database of French Society of Thoracic and Cardiovascular Surgery, and operated on between 2003 and 2020 for non-small cell lung cancer in a curative intent. The primary endpoint was overall survival up to 5 years. We assessed prognostic significance of available variables using Cox modelling, in the whole dataset, and in men and in women separately, and performed temporal validation. Finally, we constructed two sex-specific nomograms. Survivals by fifths of score were assessed in the development and temporal validation sets. Findings: The study included 62,633 patients (43,551 men and 19,082 women). Median survival time was 9.2 years. Nine factors had strong prognostic impact and were used to construct nomograms. The optimism-corrected c statistic for the prognostic score was 0.689 in the development sample, and 0.726 (95% CI 0.718-0.735) in the temporal validation sample. All differences between adjacent fifths of score were significant (P < 0.0001). Figures of 3-year OS by fifths of score were 92.2%, 83.0%, 74.3%, 64.0%, and 43.4%, respectively, in the development set and 93.3%, 88.4%, 81.0%, 73.7%, 55.7% in the temporal validation set. Performance of score was maintained when stratifying by stage of diseases. Interpretation: In the present work, we report evidence that long-term overall survival after resection of NSCLC can be predicted by an easy to construct and use composite score taking into account both host and tumour related factors. Funding: Epithor is funded by FSTCVS.

Immune changes in hilar tumor draining lymph nodes following node sparing neoadjuvant chemoradiotherapy of localized cN0 non-small cell lung cancer.

Background: While much progress has been accomplished in the understanding of radiation-induced immune effects in tumors, little is known regarding the mechanisms involved at the tumor draining lymph node (TDLN) level. The objective of this retrospective study was to assess the immune and biological changes arising in non-involved TDLNs upon node sparing concurrent chemoradiotherapy (CRT) of non-small cell lung cancer (NSCLC) tumors. Methods: Patients with proven localized (cN0M0) NSCLC, treated by radical surgery plus lymph node dissection with (CRT+) or without (CRT-) neoadjuvant chemoradiotherapy, whereby radiotherapy was targeted on the primary tumor with no significant incidental irradiation of the non-involved TDLN station (stations XI), were identified. Bulk RNA sequencing of TDLNs was performed and data were analyzed based on differential gene expression (DGE) and gene sets enrichment. Results: Sixteen patients were included and 25 TDLNs were analyzed: 6 patients in the CRT+ group (12 samples) and 10 patients in the CRT- group (13 samples). Overall, 1001 genes were differentially expressed between the two groups (CRT+ and CRT-). Analysis with g-profiler revealed that gene sets associated with antitumor immune response, inflammatory response, hypoxia, angiogenesis, epithelial mesenchymal transition and extra-cellular matrix remodeling were enriched in the CRT+ group, whereas only gene sets associated with B cells and B-cell receptor signaling were enriched in the CRT- group. Unsupervised dimensionality reduction identified two clusters of TDLNs from CRT+ patients, of which one cluster (cluster 1) exhibited higher expression of pathways identified as enriched in the overall CRT+ group in comparison to the CRT- group. In CRT+ cluster 1, 3 out of 3 patients had pathological complete response (pCR) or major pathological response (MPR) to neoadjuvant CRT, whereas only 1 out of 3 patients in the other CRT+ cluster (cluster 2) experienced MPR and none exhibited pCR. Conclusion: Neoadjuvant node sparing concurrent CRT of NSCLC patients is associated with distinct microenvironment and immunological patterns in non-involved TDLNs as compared to non-involved TDLNs from patients with non-irradiated tumors. Our data are in line with studies showing superiority of lymph node sparing irradiation of the primary tumor in the induction of antitumor immunity.

Phenotypic and Histological Distribution Analysis Identify Mast Cell Heterogeneity in Non-Small Cell Lung Cancer.

Mast cells (MCs) are multifaceted innate immune cells often present in the tumor microenvironment (TME). However, MCs have been only barely characterized in studies focusing on global immune infiltrate phenotyping. Consequently, their role in cancer is still poorly understood. Furthermore, their prognosis value is confusing since MCs have been associated with good and bad (or both) prognosis depending on the cancer type. In this pilot study performed on a surgical cohort of 48 patients with Non-Small Cell Lung Cancer (NSCLC), we characterized MC population within the TME and in matching non-lesional lung areas, by multicolor flow cytometry and confocal microscopy. Our results showed that tumor-associated MCs (TAMCs) harbor a distinct phenotype as compared with MCs present in non-lesional counterpart of the lung. Moreover, we found two TAMCs subsets based on the expression of CD103 (also named alphaE integrin). CD103+ TAMCs appeared more mature, more prone to interact with CD4+ T cells, and located closer to cancer cells than their CD103- counterpart. In spite of these characteristics, we did not observe a prognosis advantage of a high frequency of CD103+ TAMCs, while a high frequency of total TAMC correlated with better overall survival and progression free survival. Together, this study reveals that TAMCs constitute a heterogeneous population and indicates that MC subsets should be considered for patients' stratification and management in future research.

Predictive factors and prognosis of microscopic residual disease in non-small-cell lung cancer surgery.

OBJECTIVES: We described patients with microscopic residual disease (R1) operated on for non-small-cell lung cancer (NSCLC) and investigated predictive factors for R1. We also examined prognostic factors for overall survival in these patients. METHODS: From June 2003 to December 2019, a total of 2595 patients benefited from an anatomical resection operation for NSCLC in our department. All preoperative data were prospectively collected in Epithor, the French thoracic surgery national database. All pre-, per- and postoperative care followed the current recommendations. Tumours were classified by experienced pathologists according to the TNM classification and the resection status R. Survival information was collected retrospectively using the French national death register. RESULTS: A total of 94 R1 patients (3.6%) and 2255 R0 patients (86.9%) were identified. R1 patients showed significant differences: They were older (p = 0.02), with a high rate of pneumonectomy(p < 0.001), more squamous cell carcinomas (p < 0.001) and more cases of advanced-stage disease (p < 0.001). We proved that incomplete resection was a poor and independent prognostic factor whereas complete resection had a significant impact on overall survival (HR: 4.66 [3.46-6.27]). Thus, we identified high clinical T status (odds ratio [OR]: 8.82 [5.00-15.56]), high clinical N status (OR: 3.54 [2.13-5.87), squamous cell carcinoma (OR: 3.86 [2.33-6.42]), obesity (OR 1.91 [1.04-3.52]) and low forced expiratory volume in 1 s (OR: 3.62 [1.70-7.68]) as risk factors for R1. No statistical differences were found according to the location of positive resection margin or treatment, whether adjuvant or neoadjuvant. CONCLUSIONS: Incomplete resection was a poor prognostic factor for overall survival of patients operated on for NSCLC, particularly in the advanced stages of the disease. Identification of different predictive factors should help to avoid this situation.subj collection: 152.

Assessment of lung ultrasound for early detection of respiratory complications in thoracic surgery.

BACKGROUND AND OBJECTIVES: To assess lung ultrasound for the diagnosis and monitoring of respiratory complications in thoracic surgery. METHODS: Prospective observational study in a University hospital, single institution. Adult patients scheduled for pulmonary resection surgery excluding pneumonectomy. An ultrasound follow-up was performed from the day before the surgery to the third day after surgery with calculation of B-line and lung score (reaeration and loss of aeration scores). Respiratory complications were collected throughout the hospitalization period. RESULTS: Fifty-six patients were included. Eighteen patients presented a respiratory complication (32%), and they presented significantly higher BMI and ASA scores. Patients operated by videothoracoscopy were less at risk of complications. At day 3, a reaeration score ≤ 2 on the ventilated side or ≤ -2 on the operated side, and a B-line score>6 on the operated side were in favor of a complication. CONCLUSION: Lung ultrasound can help in the diagnosis of respiratory complications following pulmonary resection surgery.

Neoadjuvant durvalumab for resectable non-small-cell lung cancer (NSCLC): results from a multicenter study (IFCT-1601 IONESCO).

BACKGROUND: The IONESCO (IFCT-1601) trial assessed the feasibility of neoadjuvant durvalumab, for early-stage resectable non-small-cell lung cancer (NSCLC). METHODS: In a multicenter, single-arm, phase II trial, patients with IB (≥4 cm)-IIIA, non-N2, resectable NSCLC received three doses of durvalumab (750 mg every 2 weeks) and underwent surgery between 2 and 14 days after the last infusion. The primary endpoint was the complete surgical resection rate. Secondary endpoints included tumor response rate, major histopathological response (MPR: ≤10% remaining viable tumor cells), disease-free survival (DFS), overall survival (OS), durvalumab-related safety, and 90-day postoperative mortality (NCT03030131). RESULTS: Forty-six patients were eligible (median age 60.9 years); 67% were male, 98% were smokers, and 41% had squamous cell carcinoma. Regarding tumor response, 9% had a partial response, 78% had stable disease, and 13% had progressive disease. Among the operated patients (n=43), 41 achieved complete resection (89%, 95% CI 80.1% to 98.1%)), and eight achieved MPR (19%). The 12-month median OS and DFS rates were 89% (95% CI 75.8% to 95.3%) and 78% (95% CI 63.4% to 87.7%), respectively (n=46). The median follow-up was 28.4 months (12.8-41.1). All patients in whom MPR was achieved were disease-free at 12 months compared to only 11% of those with >10% residual tumor cells (p=0.04). No durvalumab-related serious or grade 3-5 events were reported. The unexpected 90-day postoperative mortality of four patients led to premature study termination. None of these four deaths was considered secondary to direct durvalumab-related toxicity. CONCLUSIONS: Neoadjuvant durvalumab given as monotherapy was associated with an 89% complete resection rate and an MPR of 19%. Despite an unexpectedly high rate of postoperative deaths, which prevented us from completing the trial, we were able to show a significant association between MPR and DFS.

Prevention of skin flap necrosis by estradiol involves reperfusion of a protected vascular network.

Although 17beta-estradiol (E2) is protective in experimental models of myocardial and brain ischemia, its effect on skin ischemia remains unknown. Here, we assessed the protective effect of E2 in a mouse model of skin ischemia, mimicking the surgery of skin flaps. Whereas necrosis appeared in the half portion of the skin flap within 1 week after surgery in ovariectomized mice, it was reduced up to 10-fold when mice were pretreated with E2, at least 3 days before the surgery. The beneficial effect of E2 appeared to be attributable to an increase in skin survival, revealed by measuring viability of ex vivo explants and enhancement of the antiapoptotic Bcl-2 protein expression in vivo. This protective effect on the skin contributed to the protection of the vascular network and facilitated reperfusion, which was found to be accelerated in ovariectomized E2-treated mice, whereas hemorrhages were observed in untreated mice. E2 also increased expression of fibroblast growth factor-2 isoforms in the skin and circulating vascular endothelial growth factor in the serum. Finally, this protective effect of E2 was abolished in estrogen receptor-deficient mice (ERalpha(-/-)) but maintained in chimeric mice reconstituted with ERalpha-deficient bone marrow, indicating dispensable action of E2 in bone marrow-derived cells. This protective effect of E2 was mimicked by treatment with tamoxifen, a selective estrogen receptor modulator. In conclusion, we have demonstrated for the first time that E2 exerts a major preventive effect of skin flap necrosis through a prevention of ischemic-induced skin lesions, including those of the vascular network, which contributes to accelerate the reperfusion of the skin flap.

Distinct Outcomes of Oropharyngeal Squamous Cell Carcinoma Patients after Distant Failure According to p16 Status: Implication in Therapeutic Options.

INTRODUCTION: Recent modifications in the epidemiology of oropharyngeal squamous cell carcinoma (OSCC) have led to the increase of Human papillomavirus (HPV) related metastatic head and neck cancer patients with high life expectancy even at advanced stage, low comorbidity and still restricted systemic therapy opportunities. In the recent era of ablative therapies' development, oligometastatic HPV OSCC patients are indubitably good candidates for intensified treatment. However, data related to outcomes after optimised management of metastatic sites are dramatically missing. MATERIALS AND PATIENTS: In our cohort of 186 unselected consecutive OSCC patients treated with curative intent at our institution between 2009 and 2013, we analysed the incidence, treatment and outcomes of distant metastatic (DM) failure according to p16 status. RESULTS: After a median follow-up of 4.2 years (95% CI: 3.8-4.4) from primary diagnosis of OSCC, 21/95 p16- patients (22.1%) vs. 8/91 (8.8%) p16+ patients presented DM failure with a median interval of 11 (range 0-46) and 28 months (range 0-71), respectively (p = 0.10). Overall survival (OS) after DM failure was significantly higher in p16+ patients with a two-year OS rate of 75% and 15% for p16+ and p16-, respectively (p = 0.002). In eight HPV-related metastatic patients, three underwent ablative lung metastasis treatment and are still complete responders four to five years later. CONCLUSION: This study highlights distinct outcomes of metastatic HPV-related OSCC patients emphasised by three long-term complete responders after lung ablative treatment. In patients with high life expectancy and limited tumour burden, the question of ablative treatment such as metastasectomy or stereotactic ablative radiotherapy (SBRT) should be addressed.