Locally Advanced Research Articles

Neoadjuvant therapy for localized pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor with poor prognosis and rising incidence globally. Multimodal therapy that includes surgical resection and chemotherapy with or without radiation offers the best chance for optimal outcomes. The development of established criteria for anatomic staging of local primary tumors into potentially resectable (PR), borderline resectable (BR), and locally advanced (LA) has greatly clarified the optimal treatment strategies. While upfront surgical resection was traditionally the recommended approach for localized PDAC, increasingly neoadjuvant therapy (NT) is recommended prior to surgery. Whereas NT can lead to downstaging that facilitates surgical resection for BR/LA cancers, NT also enhances patient selection for surgery, improves margin-negative resection rates, and increases the odds of completing multimodality therapy for all patients with PDAC. Herein, we review the rationale for NT for localized PDAC and summarize existing and ongoing literature.

Predicting efficacy in patients with locally advanced (LA)/metastatic urothelial carcinoma (mUC) treated with avelumab using machine learning and explainability approaches.

Predicting efficacy in patients with locally advanced (LA)/metastatic urothelial carcinoma (mUC) treated with avelumab using machine learning and explainability approaches.

Evaluating SLAM Performance with Synthesized Datasets from Unreal-Based Emulators

The rapid advancement in visual-inertial simultaneous localization and mapping (SLAM) has opened numerous applications in computer vision. However, the scarcity of high quality, publicly accessible datasets hampers the evaluation of SLAM performance in varied and tailored environments. In this study, I employed the AirSim simulator and the Unreal Engine 4 to generate a trajectory resembling that of the TUM VI Room 1 ground truth dataset within the ArchViz indoor environment representing a well-lit, furnished room. I further modified the environment and trajectory through various expansions, addition of features, and data smoothing to ensure a more stable sequence of input frames into the SLAM architecture. I then examined the efficiency of visual ORB-SLAM3 by inputting images of resolution 256×144 and 512×288 at 30 frames per second (FPS), while also adjusting the feature threshold - the maximum number of feature points that ORB-SLAM3 tracks per frame. This investigation of the camera parameters within AirSim and ORB-SLAM3 has led to the essential finding that the resolution of the input images must coincide with the dimensions of the film. The subsequent runs under these variables reveal that higher resolution images lead to considerably better tracking, with an optimal feature threshold ranging between 3000~12000 feature points per frame. Moreover, ORB- SLAM3 demonstrated significantly enhanced robustness within dynamic environments containing moving objects when using higher resolution inputs, with a decreased error of close to 0cm compared to 23.19cm for lower resolutions (averaged over three runs). Finally, I conducted qualitative testing using real-life indoor environments recorded with an iPhone Xr camera, which produces results that highlight the challenges faced by ORB-SLAM3 due to factors such as glare and motion blur.

Paclitaxel protein bound (A) plus gemcitabine (G) plus cisplatin (C) and hydroxychloroquine (HCQ) neoadjuvant therapy for localized pancreatic ductal adenocarcinoma (PDAC).

667 Background: Neoadjuvant therapy has become the consensus treatment for individuals with locally advanced (LA) and borderline resectable (BR) PDAC. Neoadjuvant therapy for resectable (R) PDAC has been in greater use due to concerns over micro metastases at diagnosis. Typical therapies involve the use of multiagent systemic chemotherapy with or without radiation therapy. In retrospective studies, Cancer Antigen 19-9 (CA 19-9) normalization in borderline resectable (BR) and locally advanced (LA) PDAC has been associated with greater OS. The addition of cisplatin (C) to gemcitabine (G) and paclitaxel protein bound (A), has shown promising clinical data in a previously reported study in advanced PDAC [JAMA Oncol. 2020;6(1):125-132]. HCQ has been shown to target autophagy in PDAC and has demonstrated higher response in combination with GA. We conducted a prospective, phase 2 clinical trial of patients with R, BR, and LA PDAC utilizing a regimen combining A + G + C + HCQ with the primary endpoint of CA 19-9 normalization (NCT04669197). Methods: Eligibility criteria include patients with histologically confirmed R, BR, or LA PDAC, elevated CA 19-9, and a KPS ≥ 70% with normal end organ function. Doses are A 125 mg/m2, G 1000 mg/m2, C 25 mg/ m2 on days 1, 8 of a 21-day cycle (IV) along with HCQ 600 mg po bid. Primary objective is to evaluate CA 19-9 normalization with the neoadjuvant chemotherapy. Secondary objectives are to assess R0 rate, pathologic complete response (pCR), safety and tolerability, radiologic response rate (by RECIST 1.1), and 2 year overall survival (OS) from date of study entry. Exploratory objectives include evaluating imaging biomarkers and vascular involvement by tumor in relation to therapy. Results: To date all planned 12 patients have been enrolled, 11 evaluable. 8 male, 4 female; age range 50 to 76 yo. Patient classifications is 3 R; 4 BR; 5 LAPC. Most common drug related grade (gr) 3-4 adverse events (AEs) are: thrombocytopenia gr 3 27%, gr 4 27%, anemia gr 3 36%, and neuropath gr 3 36%. CA 19-9 normalization occurred in 36% (4/11) who have completed at least 1 cycle of treatment. To date, 3 individuals went to surgery, with 3 achieving R0. Overall response rate in measurable patients is 45% (1CR, 4 PR). Median OS and 2-year survival data are not yet matured. Conclusions: In patients with non-metastatic PDAC, the use of A+G+C+HCQ resulted in a CA 19-9 normalization rate in 36% of individuals. Most patients did not go to surgery. The OS data is maturing. Supported by grants from the HonorHealth Foundation and Marley Foundation. Clinical trial information: NCT04669197 .

Complete Primary Pathological Response Following Neoadjuvant Treatment and Radical Resection for Pancreatic Ductal Adenocarcinoma.

Neoadjuvant treatment (NAT) for borderline (BD) or locally advanced (LA) primary pancreatic cancer (PDAC) is now a widely adopted approach. We present a case series of patients who have achieved a complete pathological response of the primary tumour on final histology following neoadjuvant chemotherapy +/- chemoradiation and radical surgery. Patients who underwent radical pancreatic resection following neoadjuvant treatment between March 2006 and March 2023 at a single institution were identified by retrospective case note review of a prospectively maintained database. Ten patients were identified to have a complete primary pathological response (ypT0) on postoperative histology. Before treatment, five patients were considered BD and five were LA according to National Comprehensive Cancer Network guidelines. All patients underwent staging Computed Tomography (CT) and nine underwent 18Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET/CT) imaging, with a mean maximum standardized uptake value (SUVmax) of the primary lesion at 6.14 ± 1.98 units. All patients received neoadjuvant chemotherapy, and eight received further chemoradiotherapy prior to resection. Mean pre- and post-neoadjuvant treatment serum Ca19-9 was 148.0 ± 146.3 IU/L and 18.0 ± 18.7 IU/L, respectively (p = 0.01). The mean duration of NAT was 5.6 ± 1.7 months. The mean time from completion of NAT to surgery was 13.1 ± 8.3 weeks. The mean lymph node yield was 21.1 ± 10.4 nodes, with one patient found to have 1 lymph node involved. All resections were reported to be R0. The mean length of stay was 11.8 ± 6.2 days. At the time of analysis, one death was reported at 35 months postoperatively. Two cases of recurrence were reported at 16 months (surgical bed) and 33 months (pulmonary). All other patients remain alive and under active surveillance. The current overall survival is 26.6 ± 20.7 months and counting. Complete primary pathological response is uncommon but possible following neoadjuvant treatment in patients with PDAC. Further work to identify the common denominator within this unique cohort may lead to advances in the therapeutic approach and offer hope for patients diagnosed with borderline or locally advanced pancreatic ductal adenocarcinoma.

Incorporating stereotactic body radiation therapy for inoperable pancreatic cancer.

656 Background: The management of inoperable pancreatic cancer (PC) is controversial. We sought to compare local progression (LP) for inoperable PC managed with chemotherapy (CHT) and/or stereotactic body radiation therapy (SBRT). Methods: This single-institution retrospective review analyzed 94 patients diagnosed with locally advanced (LA), medically inoperable, or metastatic PC between 2014 and 2022. Patients received CHT alone, sequential (seq) CHT + SBRT, or SBRT alone. The primary endpoints were LP and intervention due to local progression (ILP) from start of treatment. Obstructive symptoms needing intervention, percutaneous endoscopic gastrostomy tube, gastrojejunostomy, or bleeding needing transfusion were considered ILP. Primary tumor growth on imaging or ILP were defined as LP. Fine-Gray regression models with treatment received considered a time-varying covariate were used to compare ILP and LP between treatment groups where death without LP was treated as a competing risk adjusting for ECOG, stage, age and year of diagnosis. In the subgroup of patients who received SBRT, patients were stratified at the median time between diagnosis and receipt of SBRT, and risk of ILP and LP was compared between the groups using cause-specific cumulative incidence functions. Results: Of 94 patients, 51 had CHT alone, 21 received seq CHT + SBRT, and 22 had SBRT alone. The median year of diagnosis was 2019 (range, 2014 - 2022). The median ECOG was 1 with worse ECOG in SBRT alone and seq CHT + SBRT groups (p = 0.012). There were more LA or metastatic cases in the CHT (78%) and seq CHT + SBRT groups (67%) compared to the SBRT group (23%) [p < 0.001]. The median SBRT dose was 36Gy (range, 25 – 40Gy) in 5 fractions. Rates of LP and ILP were higher for CHT alone (68.6%, 39.2%) compared to seq CHT + SBRT (42.9%, 38.1%) or SBRT alone (18.2%, 4.5%) [p < 0.001; p = 0.004]. Higher rate of ILP associated with an increasing year of diagnosis (HR = 2.03, p < 0.005) and younger age of diagnosis (HR = 0.922, p = 0.011). The median time to SBRT was 116 days. Early (< 116 days) vs late SBRT LP rates differed (ILP: 4.8% vs 30%, LP: 14.3% vs 40%). Cause-specific cumulative incidence functions showed that death without LP favored early vs late SBRT (p = 0.009). Additionally, death without ILP favored early vs late SBRT (p=0.011). Conclusions: LP rates are high among patients with inoperable PC. SBRT for inoperable PC provides reasonable local control. Early SBRT reduces the need for ILP before death compared with late SBRT. Further investigation into the role of SBRT for inoperable PC is necessary. [Table: see text]

SKYSCRAPER-08: A phase III, randomized, double-blind, placebo-controlled study of first-line (1L) tiragolumab (tira) + atezolizumab (atezo) and chemotherapy (CT) in patients (pts) with esophageal squamous cell carcinoma (ESCC).

245 Background: Inhibition of TIGIT, a novel checkpoint inhibitor, may further amplify immune responses by complementing the PD-L1/PD-1 pathway. Anti-tumor activity has been demonstrated with cancer immunotherapy in ESCC. SKYSCRAPER-08 (NCT04540211) is evaluating the efficacy and safety of tira (anti-TIGIT) + atezo (anti-PD-L1) in combination with CT compared with placebo + CT as 1L treatment (tx) in an Asian population with unresectable locally advanced (LA), unresectable recurrent, or metastatic (R/M) ESCC. Methods: Eligible pts (confirmed LA or R/M ESCC; ECOG PS 0–1; no prior systemic tx) were randomized 1:1 to receive tira 600mg + atezo 1200mg + CT (paclitaxel 175mg/m2 + cisplatin 60–80mg/m2, local standard of care) or placebo + CT on Day 1 of each 21-day cycle (cycles 1–6); followed by tira + atezo or placebo maintenance until loss of clinical benefit/unacceptable toxicity. Primary endpoints: independent review facility (IRF)-assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints: investigator (INV)-assessed PFS, objective response rate (ORR), duration of response (DoR), and safety. Results: Overall, 461 pts were randomized (tira + atezo + CT, n= 229; placebo + CT, n=232). Pt characteristics were generally balanced between arms. As of 15 June 2022 (minimum survival follow-up 6.5 months [mo]; PFS primary analysis), median IRF-assessed PFS was 6.2 mo for tira + atezo + CT vs 5.4 mo for placebo + CT (HR 0.56; 95% CI: 0.45, 0.70; P<0.0001). As of 13 Feb 2023 (minimum survival follow-up 14.5 mo; OS final analysis), median OS was 15.7 mo for tira + atezo + CT vs 11.1 mo for placebo + CT (HR: 0.70; 95% CI: 0.55, 0.88; P= 0.0024). INV-assessed PFS, IRF-assessed ORR and DoR are presented in Table. Treatment-related adverse events (TRAEs) occurred in 98.2% of pts (both arms); Grade 3/4 TRAEs in 59.6% (tira + atezo + CT) and 56.4% (placebo + CT) of pts; Grade 5 TRAEs in 2.6% (tira + atezo + CT) and 0.9% (placebo + CT) of pts. Conclusions: The study met both primary endpoints of IRF-assessed PFS and OS, demonstrating statistically significant and clinically meaningful improvements in PFS and OS for tira + atezo + CT over placebo + CT. Generally consistent benefit was observed across subgroups, including PD-L1 status. The safety profile was consistent with the known risks of the individual tx. Clinical trial information: NCT04540211 . [Table: see text]

Impact of facility volume on outcomes in patients with pancreatic cancer treated with radiotherapy.

644 Background: The impact of facility volume on overall survival (OS) outcomes in patients with pancreatic cancer (PC) treated with radiotherapy (RT), both standard chemoradiation (CRT) and stereotactic body radiation therapy (SBRT) is not well-defined. Methods: This retrospective study analyzed 16,315 patients with locally advanced (LA) or borderline resectable (BR) PC from the National Cancer Database (2004-2019) who received neoadjuvant RT or RT without surgery across RT facilities with low- (<10 cases/yr), intermediate- (10-20 cases/yr), and high-volumes (>20 cases/yr) of PC cases. Log rank and cox regression were used for univariable and multivariable survival analysis, and Kaplan-Meier curves were generated. Results: Patients were largely treated at low (n=8055) volume centers, followed by intermediate (n=3783), and high (n=4477). Approximately half of the cohort were male (51.4%), and predominantly white (82.5%), and non-Hispanic (92%). On univariable analysis (Table), high-volume centers had improved survival outcomes in the overall population, as well as in both SBRT and CRT subsets (p<0.0001). On multivariable analysis, treatment during the most recent time period: 2016-2019 (HR 0.646, p<0.001), receiving care at a high-volume center (HR 0.844, p<0.001), use of SBRT (HR 0.915, p<0.001), administration of multiagent chemotherapy (HR 0.706, p<0.001) and undergone surgical resection (HR 0.405, p<0.001) were associated with improved OS. In a subgroup analysis of patients receiving SBRT, median OS was 22.6 months for high-volume, 20.0 for intermediate-volume and 18.4 months at low-volume centers (p<0.001). Conclusions: Patients receiving RT for LAPC or BRPC at high-volume centers had longer OS compared to those receiving radiation at intermediate- or low-volume centers. In those undergoing SBRT, treatment at high-volume centers had improved OS compared to intermediate- and low-volume centers. These findings suggest that radiation oncologists’ expertise is critical for providing high-quality RT in PC, especially for SBRT.[Table: see text]

Management of nausea and vomiting (N/V) following first-line (1L) zolbetuximab + chemotherapy treatment in claudin-18.2 (CLDN18.2)+, HER2−, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Analysis from the phase 3 SPOTLIGHT and GLOW studies.

372 Background: The phase 3 SPOTLIGHT (NCT03504397) and GLOW (NCT03653507) studies showed clinically meaningful, statistically significant improvement in PFS and OS using 1L zolbetuximab + chemotherapy vs placebo (PBO) + chemotherapy in patients (pts) with CLDN18.2+, HER2−, LA unresectable or mG/GEJ adenocarcinoma. N/V were the most common treatment-emergent adverse events (TEAEs) reported in the zolbetuximab arm of these studies. We report an analysis of the incidence and management of N/V in SPOTLIGHT and GLOW. Methods: In SPOTLIGHT, pts (N = 565) were randomized 1:1 to zolbetuximab + mFOLFOX6 vs PBO + mFOLFOX6. In GLOW, pts (N = 507) were randomized 1:1 to zolbetuximab + CAPOX vs PBO + CAPOX. In both studies, neurokinin-1 receptor blockers (NK-1), selective serotonin receptor blockers (5-HT3), and other prophylactic antiemetic regimens were recommended to prevent and mitigate N/V per institutional care and guidelines. Results: A total of 279 pts in SPOTLIGHT and 253 pts in GLOW received zolbetuximab + chemotherapy. In SPOTLIGHT and GLOW combined, nausea occurred in 58% vs 18% of pts, and vomiting occurred in 43% vs 15% of pts in the first vs second zolbetuximab infusions, respectively; lower incidences of N/V were observed thereafter. During the first zolbetuximab infusion, the first episode of N/V occurred within 1 hour (median time, 48.0 min in SPOTLIGHT and 56.5 min in GLOW). Antiemetic usage and associated N/V rates are presented in the Table. The 96 pts in SPOTLIGHT and 52 pts in GLOW who had infusion modifications in cycle 1 due to TEAEs had numerically higher infusion rates than pts without infusion modifications; 85% of these modifications in SPOTLIGHT and 79% in GLOW were due to N/V. Zolbetuximab was discontinued within the first 9 weeks in 11 and 7 pts in SPOTLIGHT and 6 and 4 pts in GLOW due to nausea or vomiting, respectively. Conclusions: In SPOTLIGHT and GLOW, slower infusion rate and use of antiemetic combinations may have helped to mitigate N/V. These strategies will be important to support continued treatment and allow pts to achieve maximum clinical benefit with zolbetuximab + chemotherapy. Clinical trial information: NCT03504397 and NCT03653507 . [Table: see text]

Local Flaps in Breast-Conserving Surgery in Early Breast Cancer Patients: Armamentarium for Breast Surgeon.

To describe the technique and outcome of local perforator arteries advancement flap in breast-conserving surgeries (BCS) in patient of early breast cancer as our initial experience and review of literature on it. Patients who underwent (BCS) with local perforator artery flap reconstruction were reviewed in terms of their clinical, surgical, and post-operative follow-up details after taking written and informed consent. We have described 4 patients of early breast cancer out of which one patient was post-NACT while 3 were for upfront BCS. We have performed LICAP in 2 patients, AICAP in 1 patient, and IMAP in one patient, depending on the location of primary tumors. None of the patients had any major or minor surgical complications in the post-operative period and drains were removed on post-operative day 2. All patients received post-operative radiotherapy and tolerated well without any loco-regional complications. Patients are in routine follow-up with cosmetic satisfaction without any local recurrence over 1year. The main advantages of pedicled perforator flaps are well-vascularized tissue, spares underlying muscle leading to lesser donor site morbidity like muscle function and seroma formation, easily reach the breast area with good match in terms of skin and subcutaneous tissue, faster recovery, and shorter learning curve in comparison to free flaps. Knowledge and skill about these flaps will help surgeon to give better surgical outcomes and satisfaction to patients.

TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes

Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate containing cytotoxic SN-38, the active metabolite of irinotecan. SG received accelerated US Food and Drug Administration approval for locally advanced (LA) or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy and a checkpoint inhibitor, based on cohort 1 of the TROPHY-U-01 study. Mutations in the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene are associated with increased adverse events (AEs) with irinotecan-based therapies. Whether UGT1A1 status could impact SG toxicity and efficacy remains unclear. TROPHY-U-01 (NCT03547973) is a multicohort, open-label, phase II registrational study. Cohort 1 includes patients with LA or mUC who progressed after platinum- and checkpoint inhibitor-based therapies. SG was administered at 10 mg/kg intravenously on days 1 and 8 of 21-day cycles. The primary endpoint was objective response rate (ORR) per central review; secondary endpoints included progression-free survival, overall survival, and safety. Post hoc safety analyses were exploratory with descriptive statistics. Updated analyses include longer follow-up. Cohort 1 included 113 patients. At a median follow-up of 10.5 months, ORR was 28% (95% CI 20.2% to 37.6%). Median progression-free survival and overall survival were 5.4 months (95% CI 3.5-6.9 months) and 10.9 months (95% CI 8.9-13.8 months), respectively. Occurrence of grade ≥3 treatment-related AEs and treatment-related discontinuation were consistent with prior reports. UGT1A1 status was wildtype (∗1|∗1) in 40%, heterozygous (∗1|∗28) in 42%, homozygous (∗28|∗28) in 12%, and missing in 6% of patients. In patients with ∗1|∗1, ∗1|∗28, and ∗28|∗28 genotypes, any grade treatment-related AEs occurred in 93%, 94%, and 100% of patients, respectively, and were managed similarly regardless of UGT1A1 status. With longer follow-up, the ORR remains high in patients with heavily pretreated LA or mUC. Safety data were consistent with the known SG toxicity profile. AE incidence varied across UGT1A1 subgroups; however, discontinuation rates remained relatively low for all groups.

Conversion surgery for initially unresectable locally advanced pancreatic ductal adenocarcinoma after chemotherapy followed by carbon-ion radiotherapy: a case report

BackgroundRecent advances in chemotherapy and chemoradiotherapy have enabled conversion surgery (CS) to be performed for selected patients with initially unresectable locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). Many studies indicate CS might extend the survival of patients with initially unresectable LA PDAC. However, several clinical questions concerning CS remain, such as the optimal preoperative treatment. Carbon-ion radiotherapy (CIRT) is a unique radiotherapy that offers higher biological effectiveness than conventional radiotherapy. Here, we report a long-term survival case with initially unresectable LA PDAC who underwent CS after chemotherapy followed by CIRT.Case presentationThe patient was a 72-year-old Japanese woman with unresectable LA pancreatic head cancer with tumor contact to the superior mesenteric artery (SMA). She underwent four courses of chemotherapy (gemcitabine plus nanoparticle albumin-bound paclitaxel). However, the lesion did not shrink and tumor contact with the SMA did not improve after chemotherapy. Because the probability of achieving curative resection was judged to be low, she underwent radical dose CIRT, and chemotherapy was continued. She complained of vomiting 2 months after CIRT. Although imaging studies showed no tumor growth or metastasis, a duodenal obstruction which was speculated to be an adverse effect of CIRT was observed. She could not eat solid food and a trans-nasal feeding tube was inserted. Therapeutic intervention was required to enable enteral nutrition. We proposed several treatment options. She chose resection with the expectation of an anti-tumor effect of chemotherapy and CIRT rather than course observation with tube feeding or bypass surgery. Therefore, subtotal-stomach-preserving pancreatoduodenectomy with portal vein resection was performed as CS. Pathological examination of the resected specimen revealed an R0 resection with a histological response of Evans grade IIA. Postoperatively, she recovered uneventfully. Adjuvant chemotherapy with tegafur/gimeracil/oteracil (S1) was administrated. At the time of this report, 5 years have passed since the initial consultation and she has experienced no tumor recurrence.ConclusionsThe present case suggests that multidisciplinary treatment consisting of a combination of recent chemotherapy and CIRT may be beneficial for unresectable LA PDAC. However, further studies are required to assess the true efficacy of this treatment strategy.

Aesthetic Considerations of Simultaneous Reconstruction With Free Flap for Local Advanced Hypopharyngeal Combined With Cervical Esophageal Cancer.

Patients with local advanced hypopharyngeal combined with esophageal cancer often require total laryngectomy and cervical esophagectomy, which result in big-sized upper aerodigestive tract defects and neck deformities. Although free flap is widely used to reconstruct aerodigestive defects, the aesthetic results especially that of neck contour have not brought to the forefront or discussed extensively. This article aims to report the preliminary aesthetic results of free flap reconstruction for local advanced hypopharyngeal cancer combined with cervical esophageal cancer defects, highlighting the thickness of subcutaneous fat of the flap. A retrospective study of 21 patients with local advanced hypopharyngeal combined with cervical esophageal cancer from July 2010 to August 2022 was conducted. After completing total laryngectomy, bilateral neck dissection, and removal of the tumor with safe margin, a free thigh flap of subcutaneous fat greater than 1 cm in thickness was used to reconstruct the hypopharyngeal and cervical esophageal defects. In addition to general demographic, oncological, and reconstructive data, preoperative and postoperative neck circumferences were recorded and compared. A subjective questionnaire survey was conducted on patients' satisfaction with postoperative neck contour. The patients were followed up from 3 to 10 years, with an average of 3 years. There were 2 cases (2/21) of free flap loss because of flap necrosis and secondary repair with a pedicled pectoralis major flap. Nineteen flaps (19/21) survived. Three cases (3/21) developed a pharyngeal fistula and one case (1/21) experienced salivary fistula, all of the fistulae healed after drainage and dressing change. There was a relatively high satisfaction rate among patients (16/21) with the postoperative neck contour. A paired sample t test showed no statistically significant difference between the preoperative and postoperative values ( t = 2.002, P > 0.05). Patients with a thicker subcutaneous fat flap (≥1.5 cm) had a more symmetrical and fuller neck contour during long-term postoperative follow-up. The application of a fat-rich subcutaneous free thigh flap to reconstruct the defect of local advanced hypopharyngeal combined with cervical esophageal cancer can achieve better neck aesthetic contour.

DOSIMETRIC AND EARLY CLINICAL OUTCOMES OF THYROID-SPARING VOLUMETRIC MODULATED ARC RADIOTHERAPY IN LOCALLY ADVANCED HEAD AND NECK CANCERS.

Radiation-induced hypothyroidism is a well-recognized entity that occurs after an interval of 15-21 months. However, in the treatment of locally advanced Head and neck Squamous cell carcinoma (HNSCC), thyroid-sparing techniques are infrequently employed. To evaluate the dosimetric and early clinical outcomes of thyroid-sparing SIB-VMAT technique (Simultaneous Integrated Boost - Volumetric Modulated Arc Radiotherapy) in patients of locally advanced HNSCC. In this two-arm prospective pilot study, patients in the study group received radiotherapy by SIB-VMAT technique with a thyroid constraint to a dose of 70 Gy to the gross disease and 59.4 Gy to nodal and subclinical disease in 33 fractions over 6 ½ weeks with concurrent cisplatin. V50Gy<75% was the thyroid constraint used. The control group was treated with the same dose and technique but without using a thyroid gland constraint. The dose-volume parameters of the thyroid gland, PTV (Planning Target Volume) along with thyroid profile were analyzed. Twenty-six patients were recruited. Thyroid V50Gy of the study group (65.33 ±6.63 %) was significantly lower than that of control group (80.35 ±13.40 %) (p=0.003). Tumor dose parameters of both groups were compared and revealed no significant difference. At 18 months follow-up, the incidence of any degree of hypothyroidism was 46.15% in the study group and 23.07% in the control group (p=0.216). In locally advanced HNSCC, it is feasible to spare the thyroid gland without compromising the tumour coverage. This has the potential to reduce the frequency of radiation-induced hypothyroidism.

Evaluation of the results of tongue reconstruction using local flaps following partial glossectomy.

Tongue reconstruction results following partial glossectomy using primary closure and local tissue rearrangement were evaluated in this study. 7 patients diagnosed with tongue carcinoma were included. Tongue defects were reconstructed using local transposition, advancement and rotation of the remaining tongue tissue and closure of the defect. The patients were evaluated 6 months and 1 year following the surgery. None of the patients had permanent speech impairments or major swallowing problems following the surgery despite 33% to 50% reduction in tongue length. Unnecessary utilization of microvascular flaps for partial tongue reconstruction should be avoided in partial glossectomy patients in which reduction in tongue length is below 50%.

Pd-L1 Evaluation in Serum and Tumoral Circulating Extracellular Vescicles in Locally Advanced Nsclc After Concomitant Chemoradiation: A Surrogate of Tumor Microenviroment Change from Cold Tumor to Hot Tumor

Background: Pacific trial has revolutioned the outcome and the approach in locally advanced (LA) unresectable Non Small Cell Lung Cancer (NSCLC). In 2018 the European Medicine Agency (EMA) approved the use of Durvalumab only in adults whose tumours on biopsy specimen expresses PD-L1 on ≥ 1% of tumour cells despite this cut-off was not provided by the original randomised study. In vitro and in vivo studies have recorded the up regulation of PD-L1 expression in the tumor microenviroment (TME) after chemoradiation regrdless the expression on biopsy. Liquid biopsy could be helpful in detection of circulating PD-L1 in this set. Aim of this observational multicentre prospective study is to assess on liquid biopsy the up-regulation of PD-L1on serum and tumoral circulating extracellular vescicles (cEVS) from patients with LA NSCLC not expressing the PD-L1 on biopsy and treated with concurrent chemoradiation (CCRT). Methods: Locally advanced NSCLC PD-L1 &lt; 1 % biopsy proven will be enrolled in this study. A blood sample will be taken the day before (T0), 14 days after CCRT (T1) and 1 months later (T2). Patients will be treated with CCRT with platinum-based doublet and 60-66 Gy total radiation dose. Soluble PD-L1 will be analysed by ELISA. PD-L1on cEVs will be isolated from serum and phenotyped by nanoparticle tracking analysis, microscopy and flow cytometry. The statistical significant improvement in PD-L1 expression in serum and cEVs at T0 -T1-T2 will be assessed by t-test for p= 0.05; for multiple test p-value will be corrected with FDR.

From Investment to the Environment: Exploring the Relationship between the Coordinated Development of Two-Way FDI and Carbon Productivity under Fiscal Decentralization

The governance exerted by governments plays a pivotal role not only in driving local economic advancement but also in bolstering environmental management and enhancing Carbon Productivity (CP). This paper investigates the impact of two-way Foreign Direct Investment (FDI) coordination development (DFDI) on China’s CP from the perspective of fiscal decentralization (FD). Utilizing panel data from 30 Chinese provinces spanning 2006–2020, we apply a Spatial Error Model to discern that DFDI effectively elevates CP. However, an excessively high degree of FD constrains the potential environmental performance benefits that FDI might offer. Further analysis using a Dynamic Threshold Model reveals a significant dynamic non-linearity in the impact of DFDI on CP under the threshold effect of FD. In contrast to Inward FDI (IFDI), China’s Outward FDI (OFDI) actually impedes the enhancement of CP. Our results underscore that well-calibrated FD can align economic growth with environmental sustainability. This study offers insights into policy frameworks fostering sustainable development in China and similar economies. It indicates that tailored policies are essential to mitigate the diverse environmental impacts of different FDI flows, supporting sustainable investment practices.

Assessing Spatio-Temporal Variation and Associated Factors of Forest Fragmentation from Morphological Spatial Pattern Analysis and Geo-Detector Analyses: A Case Study of Xinyu City, Jiangxi Province of Eastern China

In the context of economic boom and climate change, monitoring the spatio-temporal dynamics of forest fragmentation induced by disturbances and understanding its corresponding associated factors are critical for developing informed forest management strategies. In this study, based on multi-temporal Landsat images acquired from 1999 to 2020, a SVM classifier was first applied to produce high-accuracy land cover maps in Xinyu City. Next, morphological spatial pattern analysis (MSPA) was implemented to characterize the spatio-temporal patterns of forest fragmentation by producing maps of seven fragmentation components, including the core, islet, perforation, edge, bridge, loop, and branch. Then, both natural and human factors responsible for the observed forest fragmentation dynamics were analyzed using the geo-detector model (GDM). The results showed that over the past two decades, Xinyu City experienced a process of significant forest area loss and exacerbating forest fragmentation. The forest area decreased from 1597.35 km2 in 1999 to 1372.05 km2 in 2020. The areal ratio of core patches decreased by 8.49%, and the areal ratio of edge patches increased by 5.98%. Spatially, the trend of forest fragmentation exhibited a progressive increase from the southern and northern regions towards the central and eastern areas. Large-scale forest core patches were primarily concentrated in the northwestern and southwestern regions, while smaller core patches were found in the eastern and central areas. Notably, human activities, such as distance from the roads and land use diversity, were identified as significantly associated with forest fragmentation. The interaction effect of these factors had a greater impact on forest fragmentation than their individual contributions. In conclusion, Xinyu City possesses the potential to further alleviate forest fragmentation by employing the regional differentiation development strategies: (1) intensive development in the northwest and southern regions; (2) high-density development in the western, northwestern, and southern regions, and (3) conservation development in the southwest, northeast, and east-central regions, thus aligning with the path of local social advancement.

Retracted: Evaluation of the Risk of Recurrence in Patients with Local Advanced Rectal Tumours by Different Radiomic Analysis Approaches

Retracted: Evaluation of the Risk of Recurrence in Patients with Local Advanced Rectal Tumours by Different Radiomic Analysis Approaches

Primary Epithelioid Sarcoma of Frontotemporal Scalp: a Rare Case Report with Recent Literature Review

Epithelioid sarcoma (ES) is a very rare and aggressive mesenchymal sarcoma subtype which represents less than 1% of soft tissue sarcomas (STS). According to the origin of the site, there are two types of ES: distal-type epithelioid sarcoma and proximal-type epithelioid sarcoma. The clinical diagnosis of ES mainly is confirmed by histopathology examination followed by immunohistochemistry. Radical excisional surgery is the best treatment option for epithelioid sarcoma. According to TNM staging, the treatment option will vary from surgery to surgery accompanied with radiotherapy and chemotherapy. Here in, we presented a 36-year-old man had non-healing ulcer in left frontotemporal scalp extending to involve left orbit. Histopathological confirmed epithelioid sarcoma. Magnetic Resonance Imaging (MRI) of Head and Neck revealed that there was mass in left frontotemporal scalp measuring 6.7 X 5.7 X 2.6 cm extending to zygomatic region and left orbit D/D malignant mass/sarcoma with bilateral (B/L) sinusitis. After that patient undergone for Wide Local excision (WLE) surgery on 11th September 2022. Adjuvant Radiation Therapy (RT) 6000 cGy radiation dose in 30 fractions (#) which was 200 cGy per fraction (#) were given during 22nd September to 10th November 2022 due to local advancement of disease. Patient was asked to follow up after 6 weeks after completion of RT. After 6 weeks of surgery, the patient was undergone for MRI and report revealed normal study.