Level Ib Research Articles

The Emerging Theoretical Framework of Two-Person Neuroscience

Whether the submandibular gland (SMG) can be preserved during neck dissection in the surgical treatment of oral squamous cell carcinoma (OSCC) is controversial. This study investigated the SMG involvement rate and provides a basis for preserving the SMG during neck dissection in appropriate cases of OSCC.A comprehensive systematic review was conducted on the PubMed and MEDLINE, Embase, and Cochrane Library databases for studies on SMG involvement in OSCC published before December 2017 with a data analysis technique. Predictor variables were numbers of patients and resected SMGs, primary site, and tumor, node, and metastasis stage. Outcome variables were the number of involved SMGs and mode of involvement. Other variables, namely first author, publication year, mean age, and condition of neck lymph nodes at level Ib, also were extracted. A random-effects model was used to analyze the rate of SMG involvement in OSCC.Twelve studies involving 2,126 patients with OSCC who underwent neck dissection were included in the study. Fifty-two SMGs were involved, and the pooled involvement rate was 2% (I2 = 73%; 95% confidence interval [CI], 1-3). Forty-eight SMGs were involved through direct spread from the primary site or extracapsular spread of positive lymph nodes, and the pooled involvement rate was 1.9% (I2 = 72%; 95% CI, 0.9-3.1). Except for direct spread, 4 SMGs were involved through the intraglandular lymph node or carcinoma growing along Wharton ducts, and the pooled involvement rate was only 0.1% (I2 = 0%; 95% CI, 0-0.2).The rate of SMG involvement in OSCC is very low, and the most common mode of involvement is by direct spread. The SMG might be preserved during neck dissection in OSCC when it is unlikely to be involved through direct spread.

Relevance of perimarginal nodes for head and neck cancer.

To estimate the prevalence of metastasis in the perimarginal nodes (PMNs) (also known as perifacial, preglandular and retroglandual nodes) in head and neck cancer. We recruited 136 patients affected by cancers of the oral cavity, lip, oropharynx, skin and by cáncer of unknown primary (CUP), who were candidates for level IB dissection. PMNs were identified and sent separately for histological analysis. Correlation between metastasis to the PMNs and characteristics of the primary tumour were reported. The incidence of metastasis was 17% from oral cancer, 50% from lip cancer and 12.5% from skin cancer. No metastases were reported for oropharynx cancer or CUP. The only factor that correlated with the incidence of metastases was origin of the tumour from the upper part of oral cavity. PMNs represent a frequent site of metastasis in oral and lip cancers. In cancer of the oropharynx, their involvement has not been not reported, while their role in skin cancers remains to be clarified.

Predictive Factors for Submandibular Gland Involvement in Oral Cavity Squamous Cell Carcinoma-a Prospective Study from a Tertiary Cancer Center.

The oncological necessity of submandibular gland removal during neck dissection for oral cavity squamous cell carcinoma surgery has remained controversial. This study was aimed to determine the rate of SMG involvement and assess the feasibility of submandibular gland (SMG) preservation. We present a prospective study conducted at a tertiary cancer center from June 2017 to May 2019. All patients of oral squamous cell carcinoma who underwent primary surgery with neck dissection were included and analyzed for incidence and predictive factors for incidence of level IB nodal and SMG involvement as per CAP guidelines. A total of 60 patients were inducted in the study, wherein 63 neck dissections were performed including bilateral dissection in three cases. There was involvement of SMG in 6 patients with two cases each in floor of mouth cancer, gingivo-buccal, and alveolar lesions. The SMG was involved by direct contiguous spread from the primary lesion in two cases, extra-capsular extension from level IB lymph nodes in one and by both mode of spread in three glands. Perineural invasion was seen in 83.33% (n = 5) patients with SMG involvement (p- < 0.001), while 66.67% (4/6) patients had lympho vascular invasion (p-0.006) and all the cases with SMG involvement had extra-capsular extension (p < 0.001), suggesting PNI, LVI, and ECE as the strongest predictors of SMG involvement. This study demonstrates that oral cavity squamous cell carcinoma has low potential to metastasize to the SMG; however, high-risk factors include primary tumor site in floor of mouth or tongue, heavy level IB nodal burden, presence of LVI, PNI, and ECE. In the absence of these high-risk factors, SMG preservation with complete nodal clearance in level IB is a promising technique for reducing future complications.

Single-photon emission computed tomography (SPECT/CT) images of sentinel node distribution in oral cancer

This audit describes the lymphatic flow from oral tumours seen on single-photon emission computed tomography (SPECT/CT) to help sentinel node (SN) identification. A total of 95 consecutive sentinel node biopsies (SNB) were taken between 2010 and 2019. Eligibility criteria for SNB were patients over 18 years of age with a T1-T2 oral or oropharyngeal squamous cell carcinoma and an N0 neck. SNs collect at high-frequency sites irrespective of the primary tumour (22.7% level Ib; 64.8% levels II/III; and 7.6% level IV), but with individual variation. Radiotracer activity did not influence the number of nodes identified, and metastatic deposits were found in the hottest nodes. SNs occur at the same high-frequency locations in the neck, so familiarity with anatomical detail may reduce false-negative results.

Papillary carcinoma arising from thyroglossal duct cyst with cervical lymph node metastasis

Thyroglossal duct cyst carcinoma is uncommon. Its prevalence is less than one percent. Papillary carcinoma is the most common pathologic finding of the thyroglossal duct cyst carcinoma. Metastasis of the cervical lymph node is less common. Its prevalence is less than 8%. A 38-year-old woman presented with a complaint of painless mass in the midline of the neck. Ultrasonography of the neck revealed a solid cystic mass, measuring 5.5 × 2.5 cm in the submental area. Ultrasonography of the neck additionally revealed suspicion lymph node at bilateral level Ib. A preoperative Computed Tomography (CT) showed a 4 cm size MIX heterogeneous lesion in the anterior left-sided hyoid bone. The patient underwent sistrunk surgery, which was the result of the patient’s frozen section papillary carcinoma arising from the thyroglossal duct cyst. The patient had local metastasis to the neck, so she underwent total thyroidectomy and central N-D surgery and bilateral modified radical N-D. Diagnosis of thyroglossal duct cyst carcinoma before surgery is unusual. The definitive diagnosis is often after surgery and is based on the patient’s histopathological findings. The best surgical procedure is sistrunk. But if the patient has local metastasis to the neck, total thyroidectomy and modified radical N-D are performed.

Arterial blood supply patterning of the mammary sentinel lymph nodes with special reference to the relation of the formation mechanism of the superficial subscapular artery.

This study aimed to conduct a detailed anatomical examination of the arterial supply to level Ib lymph nodes corresponding to mammary sentinel lymph nodes. This was achieved by focusing on the relationship with course changes of the axillary artery trunk using 41 cadavers (49 axillae). The course patterns of the axillary artery were classified as: "Standard type," which penetrate the brachial plexus (occurrence rate, 51%); "Superficial brachial artery type," which ran along the superficial layer of the brachial plexus (2%); "Superficial subscapular artery (SSbsA) type," which entered the deep layer without penetrating the brachial plexus (42.9%); and others (4.1%). The lateral thoracic artery, thoracodorsal artery, inferior pectoral artery, and superficial thoracic artery were distributed in a regular pair relationship according to each running type of the axillary artery for the Ib lymph nodes. Comparing blood supply ratio to the Ib lymph nodes, using SSbsA occurrence as a reference, showed that significant differences were observed with the inferior pectoral artery control for the standard subscapular artery group and the lateral thoracic artery control for the SSbsA group (p < 0.0001). It was suggested that in selective modeling of vascular networks during upper limb developments, two formation tendencies occur. The standard axillary and SSbsA axillary artery trunks are induced when the inferior pectoral artery-derived feeding arteries in the superficial brachial artery system are selected for Ib lymph nodes, or lateral thoracic artery-derived feeding arteries, which are closely related to the SSbsA pathway, are acquired.

The diagnostic utility of size and apparent diffusion coefficient values for cervical lymph nodes in patients with osteomyelitis of the jaw bone.

The purpose of this study was to (1) clarify the size and apparent diffusion coefficient (ADC) value of lymph nodes (LN) in each state in their quantitative evaluation diffusion-weighted imaging, and (2) to determine the diagnostic utility of size and ADC values in the quantitative evaluation of LNs using diffusion-weighted imaging. This was a retrospective cohort study at our hospital conducted between April 2017 and March 2019. A total of 50 patients (20 men, 30 women) with 118 LNs, aged 34-90years (mean age 61.18years), undergoing magnetic resonance imaging examination were included in the study. The predictor variable was disease status. The primary outcome variable was the mean size and ADC values of the LNs. The other variables were age and sex. Data were analyzed using a Kruskal-Wallis test, and hoc Mann-Whitney tests with Bonferroni adjustment and a receiver operating characteristic (ROC) curve. P < 0.05 was considered to indicate statistical significance. We analyzed the records of 50 patients (118 LNs) with and without osteomyelitis. Of these, 21 had acute osteomyelitis, and 16 had chronic osteomyelitis. The size and ADC values of LNs in the osteomyelitis group were significantly greater and higher, respectively, than those in the non-myelitis group (P < 0.01). ROC analysis revealed a cutoff short-axis size of 4.42 and 4.04mm for lymphadenopathy caused by osteomyelitis, corresponding to levels IB and level II, respectively. Moreover, the ADC cutoff values for the same were 0.85 and 0.86, respectively. The results suggest that size and ADC values are useful parameters for the quantitative evaluation of lymphadenopathy caused by osteomyelitis.

Correlation analysis of neck node levels in 960 cases of Nasopharyngeal carcinoma (NPC)

PurposeThe delineation of intermediate risk nodal regions (CTVn2) and low-risk nodal regions (CTVn3) base on the correlation analysis between neck node levels of NPC has not been reported. We aim to analyze the correlations between different neck node levels in 960 cases of NPC, and to provide preliminary suggestions for clinical target volume (CTV) delineation of NPC base on the correlation analysis. Methods and materialsWe retrospectively analyzed the records of 960 NPCs in our institution from 2011 to 2019. Diagnostic head and neck CTs and MRIs were reviewed. The involvements of nodal levels were evaluated according to the 2013 updated guidelines. The correlations between different levels were studied using Chi-square test and logistic regression model. ResultsThe top four levels with the highest rate of lymph node metastasis were VIIa(86.35%), IIb(84.06%), IIa(62.29%), and III(47.29%). Correlation analysis showed that lymph node metastasis in level Ib was correlated with levels IIa and III. Level IIa was correlated with levels Ib, IIb, III, and Va. Level IIb was correlated with levels IIa, III, Va, and VIIa. Level III was correlated with levels IIa, IIb, IVa, Va, Vb, VIIa, and T stage. Level IVa was correlated with levels III, IVb, and Va. Level IVb was only correlated with level IVa. Level Va was correlated with levels IIb, III, IVa, Vb, and posterior to level V (PLV region). Level Vb was correlated with levels III, Va, Vc, and PLV region. Level Vc was correlated with levels IVb, Vb, and PLV region. Level VIIa was correlated with levels IIb and III. Level VIIb had no correlations with other levels. Level VIII was correlated with levels Ib and IVb. The PLV region was correlated with levels Va, Vb, and Vc. All the above P values were <0.05. ConclusionsThis study recommends setting the related levels as CTVn2 and the unrelated levels as CTVn3. The levels of nodal spread are different in NPC patients, this study reflects the principle of individualized CTV delineation.

Off-label targeted therapy (TT) use in recurrent/metastatic NSCLC.

e18688 Background: Comprehensive genomic profiling (CGP) is an established diagnostic approach to select patients for TT. As CGP gains wide adoption, an increasing number of patients are found to harbor driver mutations for which no approved TT is available. This is often addressed through use of matched TKI and mAb approved for other mutations or anatomic sites. In this work, we examined the clinical efficacy of off-label TT in R/M NSCLC. Methods: Using a de-identified NSCLC clinico-genomic database (CGDB), we identified 6590 NSCLC patients who underwent Foundation Medicine CGP, of whom 17.8% harbored an actionable genomic alteration (GA) for which an FDA-approved TT was available and 2% (133) whose GA (MET ex-14, uncommon EGFRm, EGFR ex20ins, HER2 amp/mut, RET fusion, BRAF class 2/3) lacked an FDA-approved TT (62 in 1L and 71 in ≥2L ) who received matched off-label TT. ESMO Scale for Clinical Actionability (ESCAT) was used to grade levels of evidence. For patients who progressed on initial chemotherapy (range 2 – 9 lines, median 3), we calculated clinical efficacy using the ratio of real world PFS on targeted therapy (rw-PFS2) to rw-PFS on the last prior line of therapy (rw-PFS1) and used a cut-off of PFS2/PFS1 &gt; 1.3 to determine off-label drug efficacy. Results: Of the 133 patients reviewed, 72 were classified as ESCAT level IB (uncommon EGFRm, MET-ex14), 45 IIB (HER2m/amp, EGFR ex-20ins), 7 IC (RET fusions). PFS varied significantly by mutation and line of therapy (table 1) with uncommon EGFRm+ and MET-ex14 exhibiting best response while EGFR ex20 ins, BRAF class 2/3 and HER2 amp fared significantly worse. 55.8% of the patients (39 of 71) reached a PFS2/PFS1 ratio &gt; 1.3 (two-sided 95% CI, 45.3 % – 68.7 %), ranging from 93% in uncommon EGFRm+ down to 20% in HER2 amp and 44% in ex20ins. Conclusions: We provide real-world evidence to assess off-label TT in NSCLC. Clinical benefit derived from off-label TT is unevenly distributed across various mutations with most survival advantage accruing to specific mutations (MET-ex14 and uncommon EGFRm) at the expense of others (HER2 amp). Survival advantage was highly influenced by two factors: A) the timing of CGP with the earlier recipients of genomic profiling achieving better outcome, B) the identity of the driver mutation, highlighting the role of clinical actionability tier system to define level of evidence supporting such intervention.[Table: see text]

The submental flap – Outcomes and oncologic safety in head and neck reconstruction

IntroductionThe submental flap is a reliable alternative to free flaps in the reconstruction of cutaneous facial and oral cavity defects. The thin, pliable, easily harvested flap has minimal donor site morbidity. The flap is controversial due to the potential involvement of level I lymph nodes within the flap. We describe 40 cases of head and neck reconstruction with the submental flap following resection of various cancers, and assess the oncologic safety of this flap at our centre. AimsTo evaluate the outcomes of the submental flap and assess the oncologic safety of the flap on follow-up. Material and methodsPre-operative, post-operative and follow-up data of 40 consecutive patients with oral cavity and parotid malignancies, who underwent reconstruction with the submental flap between January 2017 and June 2019, was analysed. ResultsOral cavity defects following resection of carcinoma tongue were predominant (n = 19). Patients were considered suitable for reconstruction with the submental flap only when level Ia and Ib nodes were clinically and radiologically negative for metastasis. Neck dissection was performed in all cases, with careful dissection of all level Ib nodes along the submental perforators. Flap complications were minimal. During a mean follow-up period of 14 months, no recurrences were noted within the flap. ConclusionsThe submental flap, although not the first choice, is a reliable alternative to free flaps in the reconstruction of oral defects. However, selection of patients with clinically node negative disease is extremely important, due to the potential risk of occult metastasis.

Is Site-Specific Assessment of Neck Nodes Relevant for Neck Dissection.

To highlight the strategy of neck dissection for various subsites of oral squamous cell carcinoma. Retrospective study of 153 patients with 164 neck dissection was involved between 2010 and 2016. Predictor variables were patient demographics, biopsy reports, imaging assessment and outcome variables were type of neck dissection and reconstruction performed and histological assessment of regional metastasis to the neck in relation to various primary subsites was carried out. Out of 153 patients, 126 (82.3%) were males and 27 (17.6%) were females with male-to-female ratio being 4.6:1. The mean age among the patients was 49.9 which ranged from 20 to 80years. Lymph node metastasis was found in 22.6% of T1 and T2 tumors and 77.4% of T3 and T4 tumors. Incidence for gingivobuccal sulcus accounted for 49.6% of primary sites, tongue and floor of the mouth for 15.2%, retromolar trigone for 11.7%, lower alveolus for 8.6%, upper alveolus for 5.9%, lower lip for 3.9%, buccal mucosa for 3.3% and hard palate for 2.6%. Histologically metastasis was seen in level Ib (46%), IIa (33.1%) followed by others. Level V involvement was seen only in 5.5%. For all subsites for N0 neck, minimum level III clearance should be performed, and for positive neck in RMT region, level IV or level V clearance is warranted. Apart from subsite, other factors to be considered are tumor stage, tumor thickness (DOI) and morphological characteristics of the primary tumor. The role of lymph node metastasis, number, size, extracapsular spread, its proximity and fixity to greater vessels in the neck.

Analysis of local invasion and regional spread in malignant sublingual gland tumour: Implications for surgical planning

Malignant tumours arising from the sublingual glands are very rare, and the extent and frequency of local invasion or regional spread in malignant sublingual gland tumour (MSLT) has not been fully studied due to the disease rarity. To provide comprehensive features of local and regional spread of MSLT, we reviewed 20 surgical cases for detailed pathological analyses among 26 cases diagnosed as having primary MSLT. Adenoid cystic carcinoma (ACC) was the most common pathological subtype, followed by mucoepidermoid carcinoma. Disease-free and overall survivals at 5 years were 76.1 % and 77.7 %, respectively. High-grade malignant tumours and grade 2–3 ACC accounted for 41.7 % and 85.7 %. Clinical and pathological extraparenchymal extensions were found in 34.6 % and 80.0 %, respectively. Tumour invasion to the lingual nerve and submandibular gland/ductal system were also detected in 40.0 % and 28.6 %. The incidences of lingual nerve invasion in ACC and ACC ≥4 cm were 30.8 % and 42.9 %. Regional nodal involvement occurred in seven of 26 cases, and all metastatic lymph nodes were found in neck levels Ib and IIa. In summary, a significant portion of MSLT cases consisted of high-grade tumours and grade 2–3 ACC; therefore local invasion into adjacent structures should be cautiously evaluated in cases of MSLT.

Prevalence and distribution of cervical lymph node metastases in HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma

ObjectiveIn oropharyngeal squamous cell carcinoma (OP-SCC), the prevalence and distribution of clinical and pathological lymph node metastasis in the neck have been extensively reported. It served as the basis for consensus recommendations on the selection of the lymph node levels in the neck requiring a treatment. The objective of the study is to compare the prevalence and distribution of neck node metastases in HPV+ and HPV− OP-SCC from a large series of patients with OP-SCC who underwent a cervical lymph-node dissection (LND) as part of their treatment. MethodsThe study concentrated on OP-SCC patients treated by various neck node dissection (LND) procedures from January 2014 to December 2018 in 3 French institutions. Patients with prior head and neck cancer, prior neck surgery, the use of induction chemotherapy, or patients with carcinoma of unknown primary were excluded. HPV-status was assessed by p16 immunohistochemistry. For each patient, the clinical and the pathological nodal status, as well as the distribution of the positive nodes in each neck level (from Ia to V) were reported. ResultsTwo-hundred and sixty-three patients were included (126 p16-negative (p16−), and 137 p16-positive (p16+). The rate of clinical positive node (cN+) reached 54% and 88.3% in the p16− and p16+ groups, respectively (p < 0.001); the corresponding rate of pathological positive node (pN+) reached 61.9% and 91.2%, respectively (p < 0.001). Regarding the clinical lymph node distribution, in p16+ patients, more positive nodes were observed in the ipsilateral level IV (p = 0.003), and less positive nodes were observed in the contralateral levels III and IV (p = 0.003 and p = 0.045, respectively). Regarding the pathologic lymph node distribution in the ipsilateral neck, in the cN0 patients, no significant difference was observed between p16− and p16+ patients (p = 0.33 to 1); in the cN+ patients, the nodes were distributed in levels Ib, II, III, IV and V without differences between the p16− and the p16+ patients. In the contralateral neck of p16− patients, nodes metastases were mainly observed in levels II, III and IV, whereas for the p16+ patients, positive nodes were only observed in level II (p = 0.03). ConclusionThis study demonstrated the higher prevalence of cN+ and pN+ in p16+ OP-SCC patients, but without meaningful difference in the distribution of the lymph node drainage between p16− and p16+ OP-SCC. It indicates that no difference should be made between p16− and p16+ patients regarding the extend of neck treatment.

Indications for and extent of elective neck dissection for lymph node metastasis from external auditory canal carcinoma

ObjectivesWe aim to clarify the frequency of lymph node metastasis of external auditory canal (EAC) carcinoma, including susceptible locations, adequate extent of elective neck dissection, and the relationship between the tumor infiltration site and lymph node metastasis. Patients and MethodsFrom 2003 to 2018, 63 patients with EAC carcinoma at Tokyo Medical and Dental University Hospital were enrolled in this study. The T and N stages, locations of clinically positive lymph nodes, prognoses, and anatomic site of tumor infiltration were analyzed after treatment. ResultsClinically positive lymph node metastasis (cN+) was detected in 18 patients (28.6%), consisting of T1, T2, T3, and T4 disease in 1 (6%), 2 (22%), 8 (38%), and 7 (41%) patients, respectively. The metastatic locations were at level II in 10 patients, parotid gland nodes in 7, preauricular nodes in 5, level Ib in 3, level Va in 3, level III in 1, and superficial cervical nodes in 1. Neck recurrence was determined in two of 45 patients with clinically negative lymph nodes (cN0), with the metastatic locations being levels II, Ib, and III. Among 18 cN+ cases, neck recurrence was noted in 2 of 9 patients who underwent neck dissection. Neck lesions were found to be manageable in all five patients who underwent docetaxel, cisplatin, 5-fluorouracil, and radiation therapy (TPF-RT). No relationship was noted between the tumor infiltration site and lymph node metastasis among T3/4 canrcinoma patients. ConclusionsElective neck dissection could be indicated only in T3/4 patients with free flap reconstruction. Levels Ib to III are considered appropriate for elective neck dissection in cN0 cases. Levels Ib to III and Va indicated favorable sites, even in cases with metastasis in the parotid gland or preauricular area. Furthermore, TPF-RT could be a useful option even in cN+ cases.

Cervical lymph node metastasis in squamous cell carcinoma of the buccal mucosa: a retrospective study on pattern of involvement and clinical analysis.

Background The study was performed with an aim to map the pattern of metastasis of squamous cell carcinomas of buccal mucosa to various cervical lymph node levels and analyze its correlation with primary tumor size and histo-pathological grading. Material and Methods 254 patients with squamous cell carcinoma of the buccal mucosa treated with surgery first approach were analyzed retrospectively. The tumor size was noted from pre-operative CT Scans and were divided into early and advanced tumors. The resected specimen was studied to note the histo-pathological grading of the squamous cell carcinoma and the metastatic deposits at various lymph node levels. Results Out of 254 patients (149 females, 105 males), 145 patients showed histo-pathologically proven metastatic deposits in one or more lymph nodes out of which there were 56 patients showing occult metastasis. 78/145 patients showed metastatic involvement of level IB and/or IA lymph nodes, 31 showed involvement of level II and/or I lymph nodes, 27 showed involvement of level III with or without involvement of level I and II and 9 showed metastasis to level IV and V lymph nodes with or without level I, II or III lymph nodes. Cervical lymph node metastasis had statistically significant association with tumor size with advanced tumors showing worse pattern of metastatic spread beyond level I and II lymph nodes. As the degree of differentiation of squamous cell carcinoma reduced, they were more prone for cervical metastasis with moderately and poorly differentiated squamous cell carcinoma showing higher involvement of level III, IV and V lymph nodes. Conclusions The majority of buccal mucosa cases showed metastasis to level I, II and III lymph nodes out of which level IB and/or IA was most frequently involved. Metastasis to level IV and V lymph nodes was rare and was seen especially in patients with advanced primary tumor and poor histo-pathologic differentiation. Key words:Oral squamous cell carcinoma (OSCC), cervical lymph node metastasis, histologic differentiation, locally advanced disease.

Submandibular Gland Sparing With Level IB Irradiation In Oral Cavity Cancer

Submandibular Gland Sparing With Level IB Irradiation In Oral Cavity Cancer

Deep learning for elective neck delineation: More consistent and time efficient

Background/purposeDelineation of the lymph node levels of the neck for irradiation of the elective clinical target volume in head and neck cancer (HNC) patients is time consuming and prone to interobserver variability (IOV), although international consensus guidelines exist. The aim of this study was to develop and validate a 3D convolutional neural network (CNN) for semi-automated delineation of all nodal neck levels, focussing on delineation accuracy, efficiency and consistency compared to manual delineation. Material/methodsThe CNN was trained on a clinical dataset of 69 HNC patients. For validation, 17 lymph node levels were manually delineated in 16 new patients by two observers, independently, using international consensus guidelines. Automated delineations were generated by applying the CNN and were subsequently corrected by both observers separately as needed for clinical acceptance. Both delineations were performed two weeks apart and blinded to each other. IOV was quantified using Dice similarity coefficient (DSC), mean surface distance (MSD) and Hausdorff distance (HD). To assess automated delineation accuracy, agreement between automated and corrected delineations were evaluated using the same measures. To assess efficiency, the time taken for manual and corrected delineations were compared. In a second step, only the clinically relevant neck levels were selected and delineated, once again manually and by applying and correcting the network. ResultsWhen all lymph node levels were delineated, time taken for correcting automated delineations compared to manual delineations was significantly shorter for both observers (mean: 35 vs 52 min, p < 10−5). Based on DSC, automated delineation agreed best with corrected delineation for lymph node levels Ib, II–IVa, VIa, VIb, VIIa, VIIb (DSC >85%). Manual corrections necessary for clinical acceptance were 1.4 mm MSD on average and were especially low (<1mm) for levels II–IVa, VIa, VIIa and VIIb. IOV was significantly smaller with automated compared to manual delineations (MSD: 1.4 mm vs 2.5 mm, p < 10−11). When delineating only the clinically relevant neck levels, the correction time was also significantly shorter (mean: 8 vs 15 min, p < 10−5). Based on DSC, automated delineation agreed very well with corrected delineation (DSC > 87%). Manual corrections necessary for clinical acceptance were 1.3 mm MSD on average. IOV was significantly smaller with automated compared to manual delineations (MSD: 0.8 mm vs 2.3 mm, p < 10−3). ConclusionThe CNN developed for automated delineation of the elective lymph node levels in the neck in HNC was shown to be more efficient and consistent compared to manual delineation, which justifies its implementation in clinical practice.

Treatment outcomes after definitive radio(chemo)therapy for 17 lacrimal sac squamous cell carcinoma.

Tumors of the lacrimal sac are rare and life-threatening. Because of their rarity, no extensive clinical data on their management and prognosis exist. We investigated the application of definitive radiation therapy and its outcome in patients with lacrimal sac squamous cell carcinoma (LSSCC). We retrospectively studied 17 patients with LSSCC at a single institution between 2003 and 2017. All the patients were treated with definitive radiotherapy, and 11 patients were delivered with cisplatin-based chemotherapy. The patients' clinical records were reviewed for symptoms, pathological types, the volume and dosimetry of the tumors and their adjacent structures, radiation coverage of lymph node drainage areas, treatment outcomes, and complications from definitive radiotherapy. Median follow-up was 38.9 months, and age at diagnosis was 48 years.The 2-year and 5-year overall survival, progression-free survival, locoregional control, and disease metastasis-free survival rates were 94.1 and 84.7%, 88.2 and 73.5%, 93.8%, 94.1, and 78.4%, respectively. A total dose of 6600-7000 cGy was prescribed to the tumor. Levels Ⅰb, Ⅶa, Ⅷ, and Ⅸ were covered with the clinical target volume regardless of lymph involvement. Acute Grade 3 radiation dermatitis occurred in seven patients (17.6%), but no acute Grade 4 or Grade 5 toxicity of any type occurred. Seven (41.2%, 7/17) of the treated eyes had moderated vision impairments; 17.6% (3/17) of patients developed cataracts, and glaucoma and radiation retinopathy were found in 5.9% (1/17) of patients. Definitive radiotherapy could be a treatment option for those who refuse surgery or have unresectable LSSCC. Radiation alone is a treatment option for LSSCC.

VeSpAR trial: a randomized controlled trial comparing vessel-sparing anastomotic repair and transecting anastomotic repair in isolated short bulbar urethral strictures

BackgroundVessel-sparing anastomotic repair (vsAR) has been developed as a less traumatic alternative to transecting anastomotic repair (tAR) to treat isolated short bulbar urethral strictures. This vessel-sparing technique could result in improved functional outcomes without jeopardizing the excellent surgical outcome after (transecting) anastomotic repair. The purpose of this study is to directly compare vsAR and tAR for both surgical and functional outcomes.MethodsThis trial is a prospective, interventional, multi-center, single-blinded, 1:1 randomized, controlled, non-inferiority, phase II trial. Sample size calculation resulted in a required sample size of 100 patients (50 patients per arm). Trial participants will be randomized by an independent third party using a computer-based random sequence generator with permuted blocks of variable size. The primary objective of this trial is to show that vsAR is non-inferior to tAR in terms of failure-free survival after 24 months of follow-up, considering a non-inferiority limit of 10%. Failure is defined as the inability to pass a 16-Fr flexible cystoscope through the reconstructed area without damaging the urethral mucosa. Secondary end-points mainly include differences in postoperative complications and changes in functional outcome parameters, which will be assessed with validated questionnaires. All participants are scheduled for follow-up at 3, 12, and 24 months postoperatively.DiscussionThis trial will provide level Ib evidence about the differences in both surgical and functional outcome between vsAR and tAR, which may importantly scape the future of bulbar urethral reconstruction. Depending on the trial results, this phase II trial may generate a larger phase III trial with more statistical power and a lower alpha value.Trial registrationThis trial is registered at clinicaltrials.gov (NCT03572348) and in the Belgian Clinical Trial Registry (B670201837335). The trial was registered prospectively. Registered on 28 June 2018.

Seasonality of the Final Natufian occupation at Eynan/Ain Mallaha (Israel): an approach combining dental ageing, mesowear and microwear

The Final Natufian level Ib from Eynan/Ain Mallaha provided a large and diversified assemblage of ungulates used here to study the seasonality of game procurement. The objective of this study was to evaluate the advantage of combining two methods, dental eruption and wear, and tooth microwear. Tooth microwear results allowed us to confirm the seasonality of procurement of red and roe deer and to narrow down its duration for the gazelle and the fallow deer. Game procurement occurred throughout the year for the roe deer. Red deer were hunted in spring and summer, and gazelle in late autumn–early winter. This approach allowed us to improve the accuracy of seasonality estimates and to increase sample size by using the entire population (young and adult individuals) for each species. The few individuals that were analysed with the two methods also permitted us to characterize the diet of the population at the time of death.