Long-term outcomes and safety after reirradiation in locally recurrent nasopharyngeal carcinoma in a non-endemic area.

PURPOSE: To determine outcomes and toxicities after reirradiation for locally recurrent nasopharyngeal carcinoma (rNPC) and to apply a prognostic index in a non-endemic region. METHODS: We retrospectively reported progression-free survival (PFS), overall survival (OS), and treatment-related toxicities in patients treated with curative intent for locally rNPC. We applied the prognostic model for OS and grade 5 radiotherapy (RT)-related toxicities published by Li et al. and evaluated its prognostic accuracy by receiver operating characteristic (ROC) curve analysis. RESULTS: Between 2005 and 2018, 33 patients were treated for rNPC in our institution. Median follow-up was 60 months. The mean time to local recurrence was 75 months. Six (18%) patients had a persistent grade 3 toxicity from a previous RT course. The median re-RT dose was 66 Gy. After re-RT, 13 patients had local failure and 3 patients had metastatic recurrence. Median PFS was 18 months with a 5-year PFS rate of 29%. Median OS was 35 months with a 5-year OS rate of 37%. Grade 3 or higher toxicities rate was 74%. There were 21% grade 5 toxicities. The median time to a grade 5 toxicity was less than 6 months following re-RT. The prognostic nomogram was not predictive for OS or grade 5 toxicities. CONCLUSION: Reirradiation of rNPC is an effective treatment but is associated with a high rate of life-threatening toxicity. Stratification of patients based on their risk of developing severe toxicity is needed to select patients who will most likely benefit from re-RT.

Sentinel lymph node biopsy in cutaneous head and neck melanoma.

PURPOSE: Sentinel lymph node biopsy (SLNB) is now a standard of care for cutaneous melanoma, but it is still controversial for cutaneous head and neck melanoma (CHNM). This study aims to confirm the feasibility, accuracy and low morbidity of SLNB in CHNM and evaluate its prognostic value. METHODS: A monocentric and retrospective study on patients with CHNM treated in our tertiary care center (Gustave Roussy) between January 2008 and December 2012 was performed. The feasibility, morbidity and prognostic value of this technique were analysed. RESULTS: One hundred and twenty-four consecutive patients were included. SLNB was realized in 97.6% of the cases. No significant post-operative morbidity was observed. Nineteen percents of patients had a positive SN while only 14.3% of complete lymph node dissections (CLND) had additional nodal metastasis. The risk of recurrence after positive SN was significantly higher (69.2 vs 30.8%, p = 0.043). The false omission rate was low with 7.1%. Overall survival and disease-free survival were better in the negative SN group (82 vs 49%, p < 0.001 and 69.3 vs 41.8%, p = 0.0131). The risk of recurrence was significantly higher in the positive SN group (p = 0.043) and when primary tumour was ulcerated (p = 0.031). Only the mitotic rate of the primary tumour was associated with SN positivity (p = 0.049). CONCLUSION: As in other sites, SLNB status is a strong prognostic factor with comparable false omission rate and no superior morbidity.

Efficacy of neoadjuvant cetuximab alone or with platinum salt for the treatment of unresectable advanced nonmetastatic cutaneous squamous cell carcinomas.

BACKGROUND: Refractory locally advanced or metastatic nonmelanoma skin cancer (NMSC) is a frequent therapeutic impasse. OBJECTIVES: To address the question of the efficacy of induction therapy with cetuximab as neoadjuvant treatment for locally advanced NMSC. METHODS: From 2008 to 2013, all patients with a diagnosis of unresectable locally advanced skin squamous cell carcinoma were treated with neoadjuvant cetuximab alone (CM) or combined with a platinum salt and 5-fluorouracil (CC). Resectability, and clinical and pathological response, as well as relapse-free and overall survival were evaluated. RESULTS: Thirty-four patients, with a median age of 74·5 years, were evaluated. Twenty-five patients received CC. After three cycles of CC, 23 of 25 patients whose tumours were initially unresectable became amenable to surgery (92%). A complete histological response was observed in 15 (65%) patients. The mean progression-free and mean overall survival in operated patients were 8·5 and 26·0 months, respectively. CONCLUSIONS: There was a good response in terms of resectability and tumour control in the majority of patients, with few relapses, despite the initially poor prognosis of these tumours in this elderly group of patients. However, this therapeutic strategy needs to be validated in a prospective, randomized study.

Impact of Surgery on the Evolution of Uterine Sarcomas.

STUDY OBJECTIVE: To identify the characteristics of uterine sarcomas and assess the impact of morcellation on prognosis. DESIGN: Case-control study. (Canadian Task Force classification II-2). SETTING: Hospital Quiron-Dexeus, an academic hospital. PATIENTS: Patients with uterine sarcoma histologically diagnosed and treated in our center between 1987 and 2013. INTERVENTION: All descriptive data, including type of surgery and clinical and pathological data, were reviewed. Survival analysis was performed comparing patients with hysterectomy/myomectomy without any type of morcellation and patients with morcellation during surgery. MEASUREMENTS AND MAIN RESULTS: A total of 37 sarcomas were diagnosed during the study period. The most common symptom was metrorrhagia (50%). The indication for surgery was related to myoma growth in 40% of cases and to metrorrhagia in 37.1% of cases. Open surgery was performed in 23 patients (62.2%), and laparoscopy was performed in 9 (24.3%). Myomectomy was performed in 14 patients (37.8%), and 23 patients (62.1%) underwent hysterectomy as initial surgery. Morcellation for tumor extraction was done in 8 cases (21.6%). Survival analysis by surgical approach showed increased disease-free survival (DFS) in the laparotomy group compared with the laparoscopy group (median, 70.3 months vs 10.4 months; p = .018). Median DFS according to type of surgery was 6.3 months in morcellation cases, 11.9 months in vaginal fragmentation cases, and 149.9 months in nonmorcellated cases (p < .002). The median time to progression was shorter in morcellated cases (laparocopic and vaginal) compared with nonmorcellated cases (11.9 vs 14.9 months; p < .001). No statistically significant differences in prognosis were related to myomectomy versus hysterectomy; however, there were significants difference between morcellation and nonmorcellation cases. CONCLUSION: Taking into account the negative impact of morcellation in sarcomas, the use of this technique should be reconsidered in cases of myoma with atypical clinical presentation or symptomatology. Patients must be informed about the possibility of a nonidentified sarcoma and the possible impact on prognosis resulting from its morcellation.

Pityriasis rubra pilaris-like reaction induced by imatinib.

Imatinib, a kinase inhibitor, is currently approved for the treatment of chronic myeloid leukaemia, gastrointestinal stromal tumours (GIST), and other malignant conditions such as dermatofibrosarcoma protuberans. Treatment with imatinib is generally well tolerated, but some cutaneous adverse events (AEs), such as exanthematous papular eruptions and Stevens-Johnson syndrome have been reported. We report a case of a pityriasis rubra pilaris (PRP)-like eruption associated with this drug. Although cutaneous AEs associated with imatinib are relatively common (up to 69% of cases), no previous cases of PRP-like eruptions related to this drug have been described previously, to our knowledge.

Effectiveness and safety of psoralen-UVA (PUVA) topical therapy in palmoplantar psoriasis: a report on 48 patients.

INTRODUCTION: Palmoplantar psoriasis is an uncommon clinical form of psoriasis. Although localized to the palms and soles, it has a considerable impact on the patient's function and quality of life. OBJECTIVES: To study the effectiveness and safety of psoralen-UV-A (PUVA) therapy in palmoplantar psoriasis and investigate predictors of clinical response. MATERIAL AND METHODS: We performed a retrospective chart review of all patients with palmoplantar psoriasis treated with topical PUVA therapy at our hospital between 2008 and 2011. Data were collected on effectiveness (using physician global assessment [PGA] scores), safety, and a range of clinical, epidemiological, and treatment-related variables. RESULTS: We studied 48 patients (33 women and 15 men) with a mean age of 51 years. Treatment was considered to be effective (PGA score of 0 or 1) in 63% of cases. In addition to PUVA, systemic therapy was required in 47.9% of patients; the drug most often used was acitretin. Adverse effects were reported for 25% of patients during treatment. The most common effect was mild erythema, present in 18% of cases. CONCLUSIONS: In our experience, topical PUVA is an appropriate treatment alternative for palmoplantar psoriasis; it offers similar response rates to systemic treatments, but has a better tolerance and safety profile. Associated systemic treatment, with acitretin in most cases, improved the probability of a satisfactory response to PUVA and should be considered in patients who do not respond adequately after 8 to 10 sessions.

Occult nodal metastases in T1-T2cN0 oral squamous cell carcinoma: Correlation between sentinel node positivity and completion neck dissection analysis.

OBJECTIVES: Sentinel node procedure (SN) is a standard procedure that has shown its safety and effectiveness for T1/T2 cN0 oral squamous cell carcinoma (OSCC), with completion neck dissection (CND) for patients with positive SN. The aim of this study was to characterize the nodal involvement in a cohort of SN + OSCC. MATERIALS AND METHODS: Patients with T1/T2 cN0 OSCC with positive SN with CND were included in this single-center, prospective cohort study between 2000 and 2013. RESULTS: 54/301 patients had at least one positive SN. In 43/54 (80 %) cases, only the SN(s) were invaded; with only one SN involved (SN+=1) in 36/54 (67 %) cases. No predictive factors of nodal involvement in the CND were found considering the followings: SN micro/macrometastases, primary tumor's depth of invasion (DOI), perineural spread, lymphovascular involvement, primary tumor location, T stage and extranodal extension. The SN micrometastatic involvement (n = 22) was significantly associated with only one SN + CND- (p = 0.017). In the group of patients with unique micrometastatic involvement in the SN (n = 20/54), there was a higher isolated nodal recurrence free time (p = 0.017). CONCLUSION: 80% of T1/T2 cN0 OSCC with positive SN had no other lymph node metastases in the CND, questioning the potential benefits of this procedure. Predictive factors such as the size of the SN metastasis need to be tested to stratify the risk of positive non-SN lymph nodes leading to a personalized treatment, lowering the therapeutic morbidity while maintaining the oncologic safety.

Postgraduate oncology educational shifts during the COVID-19 pandemic: results of faculty and medical student surveys.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disrupted clinical practice, research and teaching. During peaks, virtual courses were implemented but these changes are poorly described, especially for oncology postgraduate students and faculty teachers. PATIENTS AND METHODS: We administered two surveys from June 2021 to October 2021 to students and faculty teachers (250 and 80 responses, respectively) who registered at Gustave Roussy School of Cancer Sciences (Université Paris-Saclay) during 3 consecutive university years (October 2018 to October 2021), where a major shift to e-learning was associated with COVID-19 pandemic. RESULTS: Most students were female (53%), attending physicians (50%), aged 30-39 years (54%) and 2020-2021 (66.4%) was the main year of training. Most faculty teachers were male (58%), aged 40-50 years (44%) and had participated in training for at least 3 years (83%). More than half of the students received 100% virtual training [55% versus 45% face-to-face/mixed teaching modalities; online (84%) versus remote teaching (16%)]. Only 34% of students declared >80% 'active listening' and only 16% of teachers considered e-learning to be more suitable (compared with face-to-face) for postgraduate education. Virtual teaching decreased student-teacher interactions as compared with mixed/face-to-face (lessons were sufficiently interactive for 54% students if virtual only teaching versus for 71% if other teaching modalities; P = 0.009). Teachers stated that virtual learning did not lead to any improvements in terms of attendance (68%), interaction (74%) and quality of teaching (68%). However, most faculty (76%) acknowledged that partial e-learning training should be maintained outside the pandemic, if it represents ≤50% of the whole teaching (teachers: 79% versus student: 66%; P = 0.04). CONCLUSIONS: COVID-19 accelerated the transition toward novel practices. Students and faculty teachers agreed on the need for future mixed (≤50% e-learning) teaching modalities. Adequate formation and the use of codified best newer virtual practices are required.

Survey of the knowledge and management of transient ischemic attacks among primary care physicians and nurses.

INTRODUCTION: Transient ischaemic attack (TIA) patients often report that Primary Care physicians (PCPs) and nurses are their main medical contacts after onset of symptoms in our health area. There are few studies on the knowledge and management of TIA among Community and Family Medicine professionals. MATERIAL AND METHODS: Our aim was to study the current knowledge and practice in the management of TIA patients among Primary Care physicians and nurses. A cross-sectional survey with seven questions about TIA was conducted among 640 PCPs and nurses from Primary Care centres in our health area. RESULTS: In total, 285 (46.7% PCPs) took participate in the study. Of these, 239 (83.9%) participants knew the duration of a TIA. However only 40 (14%) recognised all clinical symptoms. An urgent neuroimaging was preferred by 67%. Only 42.5% agreed that an urgent cervical duplex would be useful in these patients. Transcranial Doppler was recognised by only 35.4%. A majority (78.2%) of participants agreed that TIA patients must be admitted to hospital. PCPs had the best knowledge of TIA (odds ratio [OR] 2.138; 95% CI 1.124-4.067; P = 0.021) but there were no differences between physicians and nurses on the management of these patients. Nurses from rural Primary Care centers had the worst level of knowledge (OR 0.410; 95% CI 0.189-0.891; P = 0.024). CONCLUSION: TIA was well recognized as a medical emergency. However, knowledge of clinical symptoms of TIA must be improved.

Integra® dermal regeneration template for full thickness carcinologic scalp defects: Our 6 years' experience retrospective cohort and literature review.

BACKGROUND: The aim of the study is the use of Integra® dermal regeneration template (DRT) in scalp reconstruction after tumor resection by comparing results of literature and Gustave Roussy Institut' series of 20 patients. MATERIEL AND METHODS: A systematic review, with a PubMed search was performed using the following key words "artificial dermis OR DRT" AND "scalp". Eligible articles were selected to study patients and defects characteristics, operative modalities, and the follow up results. This case series presents the experience of immediate DRT reconstruction after scalp full thickness carcinologic surgery, in the plastic surgery service of Gustave Roussy cancer center. RESULTS: Twenty patients with primary scalp tumors underwent two steps DRT reconstruction for full thickness scalp defect. The mean surface defect was 72cm2. The mean operative combined time was 94min, with a total healing delay of 68 days. All patients successfully recovered. Five patients had minor complications (3 delayed healing and 2 DRT infections) with no need of additional surgery. Fourteen articles, totalizing n=210 patients, were included and reviewed. Reported ages ranged from 58 to 82 years old. Almost all patients were operated for oncologic resections. The mean surface defect was 73cm2. The mean follow-up was 15 months. The skin graft taking rates ranged from 95% up to 100%. CONCLUSION: In large scalp full thickness defects after cancer resection, DRT appears to be a suitable reconstruction option for patients with comorbidities, and aggressive tumors. This technique allows immediate coverage of the calvarium with short operative time and prevents from healing delay. The oncologic follow-up is no disturbed and cancer recurrences are easily diagnosed.

Replacement of lip-split mandibulotomy by pull-through approach for T3-4 oral carcinomas.

At the study hospital, the lip-split mandibulotomy (LSM) has progressively been replaced by a pull-through (PT) approach. This study compared the outcomes of the LSM and PT approaches in a series of 192 patients with T3-T4a oral tongue and floor of the mouth squamous cell carcinoma treated over the two last decades. No difference in margin status (P = 0.254), rate of early complications (local infections) (P = 0.867), haematoma/haemorrhage (P = 0.221), delayed wound healing (P = 0.438), re-operation (P = 0.083), or Clavien-Dindo classification (P= 0.5281) was found. The LSM approach was associated with a higher rate of late complications such as pseudarthrosis (14.5% vs 0.9%; OR 17.89, P = 0.0005) and trismus (35% vs 13.8%; OR 3.32, P = 0.025), and a trend towards a higher rate of fistulas (24.6% vs 13.1%; OR 2.16, P = 0.088). The quality of life of long-term survivors (median 132 months) was similar in the two groups, with a mean QLQC30 score of 59.7 (P = 0.099) and mean MDADI score of 57.4 (P = 0.213). The 5-year local control rate was 86.4% in the PT group and 86.2% in the LSM group (P = 0.878), while the 5-year overall survival rates were 50.0% and 48.3%, respectively (P = 0.68). In our experience, replacement of LSM by a PT approach in oral carcinoma was associated with decreased rates of late complications such as pseudarthrosis, fistula, and trismus, without any difference in oncological outcomes.

Predictive value of ankle brachial index in patients with acute ischaemic stroke.

BACKGROUND: The ankle brachial index (ABI) is a known measure of lower-limb peripheral artery disease (PAD), as well as a marker for other cardiovascular disease events. OBJECTIVE: Our goal was to compare the prevalence of abnormal ABI scores (ABI or=3 (33.8% vs. 7.1%, P = 0.001) and large-artery atherosclerosis (LAA) (43.5% vs. 19.4%, P = 0.015). Multivariate analyses (logistic regression) only identified VRF > 3 as independently associated with low ABI (OR: 6.46; 1.81-23.02; P = 0.004). Abnormal ABI was associated with stroke recurrence (32.1% vs. 13.6%, P = 0.027) and the appearance of any major vascular event (50.0% vs. 17.0%, P < 0.001). In the logistic regression analysis, adjusted for VRF, age, and LAA, ABI remained as an independent predictor of vascular events (HR 3.99; 1.90-8.41 P < 0.001). CONCLUSION: Abnormal ABI was associated with classical risk factors, especially hypertension. The measurement of ABI amongst patients with IS appeared to be useful to identify high-risk patients and plan adequate prevention therapies.

[Neurocutaneous flaps applied on head and neck surgery: Anatomic study of feasibility using superficial cervical plexus branches]. / Lambeaux neurocutanés appliqués à la chirurgie cervicofaciale : étude anatomique de faisabilité à partir des branches du plexus cervical superficiel.

OBJECTIVE: To evaluate the feasibility of neurocutaneous flaps for head and neck surgery using the cervical superficial plexus branches. METHODS: Anatomic study on cervical superficial plexi (focusing on the great auricular and cervical transverse nerves) of five fresh specimens, which were injected with green colored latex. RESULTS: A constancy of anatomic landmarks has been observed with little inter-individual variability. The cervical superficial plexus branches were easily isolated, their length and course not varying much. Each cervical superficial plexus nerve is accompanied by a perinervous artery, essential condition to a neurocutaneous flap. We privileged the great auricular nerve for its superior length and diameter, in order to easy the raise of the flap. We took it at the low mastoidian level, pediculed on the great auricular nerve with a point on the posterior border of the sterno-cleido-mastoidian muscle. Pedicule size is 7 to 10cm allowing to reach ipsilateral alae of the nose, the chin or the pinna. Developing this technique for oropharyngeal reconstruction (internal side of the cheek, anterior floor of mouth...), whereas not realized in this study, must be considered. CONCLUSIONS: The anatomic study showed the cervical superficial plexus constancy with the systematic presence of a perinervous pedicle siding each branch. The great auricular nerve is a good candidate for the raise of a neurocutaneous flap. A standardized surgical procedure must be established before any clinical study.

Long-term recurrences of jaw osteoradionecrosis after apparent healing with the PENTOCLO protocol.

Osteoradionecrosis of the jaws (ORNJ) is a late complication of head and neck irradiation estimated at around 3% of irradiated patients. The PENTO protocol (Pentoxyfilline and Tocopherol), with the eventual adjunction of Clodronate (PENTOCLO), showed interesting results even in advanced ORNJ. The current literature does not describe the long-term outcomes and particularly after the completion of the protocol. The PENTO or PENTOCLO protocol should be prescribed as a life-long treatment or the outcome should be monitored at least as long as the duration of the protocol after its end.

Oncologic outcomes, prognostic factor analysis and therapeutic algorithm evaluation of head and neck mucosal melanomas in France.

BACKGROUND: Head and neck mucosal melanoma (HNMM) is aggressive and rare, with a poor prognosis because of its high metastatic potential. The two main subtypes are sinonasal (sinonasal mucosal melanoma [SNMM]) and oral cavity (oral cavity mucosal melanoma [OCMM]). Consensual therapeutic guidelines considering the primary tumour site and tumour-node-metastasis (TNM) stage are not well established. MATERIAL & METHODS: Patients with HNMM from the prospective national French Rare Head and Neck Cancer Expert Network database between 2000 and 2017 were included. Clinical characteristics, treatment modalities, outcomes and prognostic factors were analysed. RESULTS: In total, 314 patients were included. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 49.4% and 24.7%, respectively, in the surgery group; no long-term survivors were observed when surgery was not feasible. Moreover, even after surgery, a high recurrence rate was reported with a median PFS of 22 months. In multivariate analysis, Union for International Cancer Control (UICC) stage and tumour site correlated with PFS and OS. Postoperative radiotherapy (PORT) improved the PFS but not OS in patients with small (T3) SNMM and OCMM tumours. Nodal involvement was more frequent in patients with OCMM (p < 10-4), although, as in SNMM, it was not a significant prognostic predictor. CONCLUSION: Even early HNMM was associated with poor oncologic outcomes due to distant metastases despite surgical resection with clear margins. Lymph node metastases had no impact on the prognosis, suggesting treatment de-escalation in cervical node management. PORT might be useful for local control.

Reconstruction of maxillectomy and midfacial defects using latissimus dorsi-scapular free flaps in a comprehensive cancer center.

BACKGROUND: The standard of care for sinonasal malignancies is a large surgical resection followed by radiotherapy. Midfacial defects resulting from maxillectomy require a complex reconstruction procedure. Given their adaptability, chimeric flaps such as latissimus dorsi-scapular (LDS) free flaps appear to be a good option. MATERIAL & METHODS: We performed a single-center retrospective study of consecutive patients with sinonasal cancers where a LDS free flap was used for reconstruction. We assessed the postoperative complications and the functional, aesthetic and oncologic outcomes. RESULTS: Eighty-four patients were included. Primary tumors were staged as T4a in 68% of cases; 38.3% of the patients received induction chemotherapy and 82.7% received adjuvant radiotherapy. Based on our classification of midfacial and palatal defects, the majority of the patients (69%) had a type IIa with interruption of the three facial pillars. The orbital floor was removed in 55.9% of cases. The median follow-up was 45 months. Total flap necrosis with no possible revascularization occurred in 5.9% of cases. For the orbital reconstruction, a revision procedure was needed for necrosis and/or infection of the costal cartilage graft in eight cases (17%). More than 90% of the patients had no functional disorders regarding speaking, swallowing and chewing. Soft palate involvement was a prognostic factor of speech (p < 10-4) and swallowing (p = .005) disorders. Dental rehabilitation was realized in 70.2% of the patients. No severe complications were observed in the donor site, except for one seroma. CONCLUSION: A LDS free flap is a reliable technique for the reconstruction of complex midfacial defects.