Site Of Recurrence Research Articles

Effectiveness of adjuvant chemotherapy for patients who undergo radical cystectomy without neoadjuvant chemotherapy: A retrospective cohort study of 115 advanced bladder cancer patients with pathological lymph node classification.

We investigated the clinical outcomes of radical cystectomy without cisplatin-based neoadjuvant chemotherapy (NAC) and identified factors affecting the effectiveness of cisplatin-based adjuvant chemotherapy (AC). Between September 2002 and February 2020, 288 bladder cancer patients who did not receive NAC underwent radical cystectomy. We retrospectively analyzed the recurrence rates, primary recurrence sites, recurrence-free survival (RFS), and overall survival (OS) of 115 advanced bladder cancer patients (pT3-4 or pN1-3) who were divided into the AC and observation groups. Subgroup analysis was performed, focusing on pathological stage. In total, 51 patients received AC, and 64 patients were observed. The median follow-up duration was 95 months. The recurrence rate was lower in the AC group than in the observation group (35.3% vs. 54.7%, p = 0.041). The rate of recurrences in the lymph node area (dissection site and proximal lymph nodes) was lower in the AC group (9.8% vs. 26.6%; p = 0.031). In the subgroup analysis of patients with pN1, the probability of RFS and OS was higher in the AC group than in the observation group. The hazard ratio for RFS and OS was 0.243 (95% confidence interval [CI]: 0.077-0.768) and 0.259 (95% CI: 0.082-0.816), respectively. The 5-year RFS and OS were significantly higher in the AC group (80.0% and 79.4%) than in the observation group (35.7% and 42.9%; p < 0.008 and p < 0.012, respectively). AC improved RFS and OS in patients with pN1 disease who did not receive NAC and should be considered for this population.

Anatomical assessment of local recurrence site in breast cancer patients after breast reconstruction and post-mastectomy radiotherapy: implications for radiation volumes and techniques.

Post-mastectomy radiotherapy (PMRT) improves local control rates and survival in patients with adverse prognostic features. The dose coverage to target volumes is critical to yield maximum benefit to treated patients, increasing local control and reducing risk of toxicity. This study aims to assess patterns of breast cancer relapse in patients treated with mastectomy, breast reconstruction and PMRT. Breast cancer patients treated with PMRT between 1992 and 2017 were retrospectively reviewed. Clinical and pathological characteristics of patients were collected. Recurrences were defined as "in field," "marginal" or "out of field." Survival analyses were performed in relation to progression-free survival (PFS) and overall survival (OS). Correlation between baseline features was explored. Data of 140 patients are collected. After a median follow-up time of 72 months, median PFS and OS of 63 and 74 months were detected, respectively. Neoadjuvant chemotherapy, lympho-vascular space invasion (LVI) and size of primary tumor were all significantly associated with worst PFS and OS. Ten patients developed local recurrence: 30% "in field," 30% marginal recurrences, 20% "out of field" and 20% both "in field" and "out of field." No recurrence was detected under the expander, 80% above the device and 20% patients relapsed on IMN chain. The mean distant relapse-free survival was 39 months. Overall, 39 of 140 patients developed distant metastases. The onset of local-regional relapses occurred mainly above the expander/prosthesis, underlying the importance of inclusion of the subcutaneous tissues within the target volume. In order to refine new contouring recommendations for PMRT and breast reconstruction, future prospective studies are needed.

Survival Outcome After Surgery in Patients With Thymoma Distant Recurrence

ObjectiveThe aim of this study is to describe characteristics and survival outcome of patients who underwent surgical treatment for distant thymoma relapse according to the definition of the International Thymic Malignancy Interest Group. MethodsData of patients affected by thymoma recurrence from four different institutions were collected and retrospectively reviewed. Patients with locoregional metastases who underwent nonsurgical therapies and with incomplete data on follow-up were excluded. According to the International Thymic Malignancy Interest Group distant recurrence definition, patients with recurrence due to hematogenic localization were included. Clinical and pathologic characteristics were described using descriptive statistics, whereas survival outcome was calculated using Kaplan-Meier curves and Cox regression analysis. ResultsThe analysis was conducted on 40 patients. A single localization was present in 13 patients, the relapse was intrathoracic in 28 cases (70%), and lung involvement was found in 26 cases. The liver was operated in seven cases, whereas other kinds of abdominal involvement were detected in eight cases. Adjuvant treatment was administered in 22 cases (55%).Five- and 10-year overall survival (OS) were 67% and 30%, respectively. Univariable analysis identified as significant favorable factor a low-grade histology (A, B1, B2): five-year OS at 92.3% versus 53.3% in high-grade (B3–C) (p = 0.035). Site of recurrence and number of localization did not influence the prognosis, but in patients with adjuvant therapy administration, there was a survival advantage also if not statistically significant: five-year OS 84.8% versus 54.5% in patients without adjuvant therapy (p = 0.101).Multivariable analysis confirmed as independent prognostic factor low-grade histology: hazard ratio = 0.176, 95% confidence interval 0.042–0.744, p = 0.018. ConclusionsOur study revealed a good survival outcome in patients who underwent surgery for distant thymoma recurrence, independently from the number and site of the relapse localization. Patients with A, B1, or B2 histology presented a significantly better survival than patients with B3-C.

Borderline tumours of ovary and fertility preservation–Outcomes from a tertiary care center in India

ObjectiveBorderline ovarian tumors (BOT) are characterized by atypical epithelial proliferation without stromal invasion and majority are diagnosed in women of reproductive age group desirous of fertility preservation. MethodsA retrospective review of medical records of patients diagnosed with BOT and on regular follow up at the All India Institute of Medical Sciences New Delhi, during a nine-year study period from March 2014 to March 2023 was performed. Surgical treatment was classified as radical or fertility sparing surgery (FSS). Surgical staging was defined as complete, partial or un-staged. ResultsMedian age of 91 women was 34 years. Follow up period ranged from 4 to 222 months (median 77 months). Among 68 premenopausal women, 31 (46 %) underwent radical surgery and FSS in 37 (54 %) cases. Median time to conception in 29 women with future fertility wishes was 13 months (range, 4 to38 m). Seven of 29 cases (29 %) required ovulation induction. The pregnancy rate was 82.7 % and live birth rate was 80 %. Eight cases (8.7 %) had a recurrence (7- un-staged, 1- partially staged) and median time to recur was 36 months. There was no significant difference in recurrence between cystectomy/oophorectomy. Ovary was the site of recurrence in all surgically salvaged cases except peritoneal cavity in 1 case with mortality. Relapse free survival at 5 and 10 years in FSS and radical surgery group were similar. ConclusionFSS is a safe procedure and should be considered in young patients desirous of future fertility along with a comprehensive peritoneal staging. Reproductive outcomes are excellent.

Comparison of Surgical Outcomes of Transoral Versus Open Thyroidectomy for Graves Disease.

The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a safe alternative to thyroidectomy for thyroid goiter and provides the benefit of being scarless. However, the data on the use of TOETVA in patients with Graves disease are limited. This retrospective study compared the outcomes of Graves disease patients who underwent TOETVA versus those who underwent open thyroidectomy (OT). Patients with Graves disease who received TOETVA or OT for bilateral total thyroidectomy between September 2017 and October 2022 were included. Patient demographics and surgical outcomes, including operation time, blood loss, length of stay, and complications, were compared. There were 15 patients in each group. The mean age in the TOETVA group was 35.80±8.13 years, which was significantly younger than that in the OT group, which was 51.53±14.22 years. Females predominated in both groups. The other demographic characteristics were similar in both groups. The operation time and intraoperative blood loss were also comparable. The postoperative stay and complications, including hypoparathyroidism, recurrent laryngeal nerve injury, surgical site infection, postoperative hemorrhage, and recurrence of hyperthyroidism, were not different between the 2 groups. There were 11 patients in the TOETVA group and 10 in the OT group who had thyroglobulin levels <0.1ng/dL, indicating the completeness of total thyroidectomy in the 2 groups. There was no conversion of TOETVA to an open procedure. For carefully selected Graves patients, TOETVA offers a safe, scarless, and feasible alternative to conventional open thyroidectomy.

Clinical Impact of the Lymphocyte-to-Monocyte Ratio in Patients With Gastric Cancer who Received Curative Treatment.

The aim of the present study was to evaluate the clinical impact of the pretreatment lymphocyte-to-monocyte ratio (LMR) on both short- and long-term oncological outcomes in patients with resectable gastric cancer (GC). The patients were chosen based on our medical records from consecutive cases of curative resection for GC performed at Yokohama City University from 2005 to 2020. The LMR was calculated as the lymphocyte count divided by the monocyte count measured before surgery. The three- and five-year overall survival (OS) rates were 63.1% and 57.4%, respectively, in the low-LMR subgroup and 86.4% and 77.5%, respectively, in the high-LMR subgroup. According to multivariate analysis, the LMR was an independent prognostic factor for OS [hazard ratio (HR)=1.926, 95% confidence interval (CI)=1.143-3.245, p=0.014]. In addition, the three- and five-year RFS rates were 54.4% and 50.7%, respectively, in the low-LMR subgroup and 84.0% and 76.0% in the high-LMR subgroup. According to multivariate analysis, the LMR was an independent prognostic factor for OS (HR=2.031, 95%CI=1.266-3.258, p=0.003). When comparing the sites of recurrence between the low-LMR and high-LMR groups, there were significant differences in hematologic recurrence, lymph node recurrence, and peritoneal recurrence. Preoperative LMR might be a promising tool for the treatment and management of GC.

Comparison of the Outcome of Surgery and Radiotherapy in the Treatment of Early Carcinoma of the Larynx

Background: The most prevalent disease to afflict the head and neck region is laryngeal cancer. The early stage of this disease, T1T2N0M0, has a higher chance of recovery than the other phases. Radiation therapy and surgery are its therapeutic techniques.&#x0D; Objective: To Compare the outcome of surgery and radiotherapy in the treatment of early carcinoma of the larynx&#x0D; Methods: This cross-sectional study was carried out at tertiary hospital Dhaka from January 2022 to January 2023. Where A total of 200 Patients of carcinoma of the larynx are evaluated properly by detailed history taking, clinical examination and relevant investigation. During the study two groups of patients were dealt separately; Group-1: Surgery using LASER, n=100 and Group-2: radiotherapy, n=200. All the patients were followed up after 2 weeks, 1 month and then three monthly for one year.&#x0D; Results: During the study, supraglottis carcinoma was found in 65% of radiotherapy group and 70% in surgery group, glottic carcinoma was 35% &amp; 30%, respectively in radiotherapy and surgery group. No case found with subglottic carcinoma. Where in surgery group 7% patients had haematoma, 5% patients had seroma &amp; pharyngeal stenosis. In radiotherapy group 2.5% Severe radiation necrosis of skin &amp; 3% had Respiratory distress following radiotherapy. . In the radiotherapy group, 25% cases were scored as normal and 45% as good. For the surgery group, 40% patients had good voice and speech, 35%r had moderate voice and speech, and 5% had poor voice and speech. This difference was statistically significant (p=.001). 14% of the irradiation group had a primary site recurrence compared with 20% in the surgery group at 12th months. There was a significant difference in the pattern of recurrence in the neck between the two treatment groups. Only 5% of those who were treated with irradiation had a recurrence in the neck. 14% of patients in the surgery group had a recurrence in the neck; this difference was statistically significant.&#x0D; Conclusions: When treating early laryngeal cancer, radiation therapy and surgery are equally successful. However, patients who had radiation therapy had much improved speech and voice quality compared to those who received surgery.

Abstract 2519: Alteration of tumor immune microenvironment after recurrence and its impact on the efficacy of anti-PD-1 antibody in resected non-small cell lung cancer patients

Abstract Background: Tumor immune microenvironment (TIME), including programmed death-1 ligand-1 (PD-L1) and CD8-positive tumor-infiltrating lymphocytes (TIL), has been suggested as a potential biomarker to predict the efficacy of anti-PD-1 antibody. Postoperative recurrence in patients with non-small cell lung cancer (NSCLC) is treated with therapeutic strategies similar to those for metastatic disease. However, in postoperative recurrence cases, PD-L1 evaluation is generally based on archival resection specimens, because there is little opportunity for a new biopsy of the recurrent site. Therefore, it remains unclear whether TIME of recurrent lesion is similar to TIME of primary lesion at surgery, and the efficacy of anti-PD-1 antibody for postoperative recurrent NSCLC patients based on TIME status at surgery is unknown. Materials and Methods: Cohort A included 59 patients with advanced and 25 patients with postoperative recurrence NSCLC who treated with first-line pembrolizumab monotherapy. PD-L1 expression and CD8-TIL were evaluated immunohistochemically in tumor specimens obtained at diagnosis in the advanced cases and at surgery in the postoperative recurrence cases. Tumor proportion score for PD-L1 and the extent of CD8-TIL were evaluated and classified as high or low. TIME was categorized into 4 subclasses, according to the respective PD-L1 and CD8-TIL, as follows: (class I) high/high; (class II) low/low; (class III) high/low; and (class IV) low/high. Progression-free survival (PFS) of pembrolizumab was compared based on TIME. Cohort B consisted of 50 NSCLC patients who underwent radical resection, and whose tumor specimens were obtained from recurrent site. As in cohort A, TIME was assessed for paired resection and recurrent tumor samples. Results: In cohort A, the median PFS of pembrolizumab for the advanced cases were 25.7 months in class I (n=25), 2.3 months in class II (n=8), 8.0 months in class III (n=20), and 6.5 months in class IV (n=6) (p&amp;lt;0.001), respectively; while those for the postoperative recurrence cases were 9.0 months (n=7), 4.3 months (n=7), 7.6 months (n=6), and 2.5 months (n=5) (p=0.55), respectively. In cohort B, TIME for resected primary lesion were observed in 9 with class I, 20 with class II, 3 with class III and 18 patients with class IV, respectively. The concordance of PD-L1 category (high vs low) between resected primary lesion and recurrent lesion was 88.0%, while that of TIME classification was 54.0%. Conclusion: TIME classification using tumor specimens just before administration of anti-PD-1 antibody was useful predictive biomarker. However, TIME alterations between resection and postoperative recurrence were observed in many cases, suggesting that TIME based on tumor specimens at surgery may not be useful for predicting the efficacy of anti-PD-1 antibody for postoperative recurrent NSCLC. Citation Format: Yoshiya Matsumoto, Tetsuya Watanabe, Megumi Mizutani, Akira Sugimoto, Hiroaki Nagamine, Yoko Tani, Kenji Sawa, Takuma Tsukioka, Hiroyasu Kaneda, Shigeki Mitsuoka, Noritoshi Nishiyama, Tomoya Kawaguchi. Alteration of tumor immune microenvironment after recurrence and its impact on the efficacy of anti-PD-1 antibody in resected non-small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2519.

Abstract 5197: Identification of novel molecular biomarkers for predicting postoperative recurrence of ampulla of Vater carcinoma

Abstract Background: Ampulla of Vater (AoV) carcinoma is a rare tumor that accounts for 20 % of periampullary cancers. Surgical resection is the only treatment that can expect cure of disease, and there is still an unmet need to predict postoperative recurrence. In this study, we investigated the novel molecular biomarkers that can predict the risk of recurrence after surgery with AoV carcinoma. Methods: In this retrospective study, we collected the surgically resected tissue and medical records of patients who were diagnosed with AoV carcinoma at Samsung Medical Center from January 2005 to December 2020. Patients were classified patients according to the initial stage and experience of tumor recurrence. Whole transcriptomic analysis using primary AOV tumor and recurred tumor tissue samples was conducted to identify the molecular biomarker for tumor recurrence. Results: A total of 40 tumor tissue from primary site in non-recurrence group, 22 tumor tissue from primary site in recurrence group, and paired 22 tumor tissue from recurrence site were analyzed. A total of 1005 genes differentially expressed between primary tumor of non-recurrence group and recurrence group were found. Gene set enrichment analysis showed that pathways related to fatty acid metabolism, adipogenesis, oxidative phosphorylation, and hypoxia were upregulated, and pathways associated with interferon gamma response, and mTOR signaling were downregulated in recurrence group. These pathways were significantly affecting the recurrence free survival which was verified with TCGA data, and we further identified some candidate genes including PIM3, IGFBP4, SLC19A1, HIF1A and CXCL11 to predict tumor recurrence . Moreover, we found candidates for single gene level biomarkers to predict early tumor recurrence in N0 stage. Low expression of UQCC3 and high expression of CLCNKB was related to early tumor recurrence. Conclusions: We found the candidates for novel molecular level biomarker to predict postoperative recurrence of AoV carcinoma. In the future, it is necessary to develop a predictive model for the risk of recurrence after surgical resection for AoV carcinoma. Citation Format: Hyemin Kim, Jin Ho Choi, Hyoung-oh Jeong, Aryoung Kim, Se-Hoon Lee, Kwang Hyuck Lee, Kyu Taek Lee, Jong Kyun Lee, Semin Lee, Joo Kyung Park. Identification of novel molecular biomarkers for predicting postoperative recurrence of ampulla of Vater carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5197.

Abstract 5072: Multi-omic, multi-scale characterisation of colorectal cancer defines spatiotemporal patterns of recurrence

Abstract Aim: Patients who undergo intended curative resection of colorectal cancer (CRC) have a 20-25% chance of metachronous recurrence, the site and timing of which are unpredictable and resistant to current treatment. The biological basis for such heterogeneous disease behavior remains to be elucidated. Bulk transcriptomic profiling and subsequently single-cell RNAseq have provided insight in the epithelial subtypes and immune microenvironment. Recently spatially resolved transcriptomic assessment allow molecular profiling of tissue while preserving tissue architecture. Utilizing ST technology we sought to perform deep characterization of a large cohort of patients with primary CRC with the intention to decipher the biological determinants of spatio-temporal patterns of recurrence. Methods: 750 patients who underwent resection of CRC with mature follow up were studied. Bulk transcriptomic, genomic and multiplex immune characterization was performed using a TMA format. Of these, 28 patients were assessed using single cell spatial transcriptomics (Nanostring CosMx Spatial Molecular Imager (SMI, 1000plex gene panel)), 120 tumors underwent regional whole transcriptome profiling of epithelium and TME (Nanostring GeoMx Digital Spatial Profiler using FFPE tissue). We used image analysis and bioinformatics to integrate these complex datasets in over 120000 single-cells in the context of their spatial tissue architecture and clinicopatholgical outcome and recurrence data. Results: Using the CosMx SMI we characterized cells with complete topographic detail and defined 2 unique epithelial cell states defined. Each epithelial state had distinct spatial properties including cell size and morphology, average distance to nearest lymphocyte, neighboring cell types and stromal neighborhood. This epithelial signature was integrated in GeoMx samples and were found to predict recurrence (p&amp;lt;0.05). The Epithelial, Fibroblast and Immune GeoMx transcriptomic compartments were expanded and grouped using unsupervised clustering. Each compartment demonstrated groups of patients where specific spatially derived signatures could predict site and time of recurrence (p&amp;lt;0.05). Conclusions: By maintaining the tissue structure, we have directly measured cellular interactions and captured cells commonly missed during dissociative studies whilst defining novel molecular subtypes of CRC with clinical relevance. Novel platforms such as CosMx allow deeper characterization of unique cell types and cellular interactions that may pave the way for novel therapeutics and precision medicine for patients with CRC. Citation Format: Colin Stuart Wood, Joao Da Silva Filho, Andrew Cameron, Assya Legrini, Holly Leslie, Tengyu Zhang, Yoana Doncheva, Claire Kennedy-Dietrich, Matthias Marti, Joanne Edwards, Paul Horgan, Campbell Roxburgh, Colin Steele, Nigel Jamieson. Multi-omic, multi-scale characterisation of colorectal cancer defines spatiotemporal patterns of recurrence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5072.

Abstract 974: DNA methylation and gene expression as determinants of genome-wide cell-free DNA fragmentation

Abstract Cell-free DNA (cfDNA) in the bloodstream is increasingly gaining attention as a diagnostic tool for the early detection of cancer. Nevertheless, the characteristics and sources of cfDNA fragmentation in the blood remain poorly understood. In this study, we sought to unravel the impact of DNA methylation and gene expression on the naturally occurring genome-wide fragmentation of cfDNA. We performed a comprehensive analysis of plasma samples from 969 individuals, including 182 individuals diagnosed with cancer (pancreatic, colorectal, ovarian, lung and breast cancer). In healthy individual cfDNA fragmentation patterns like DNA motifs at cfDNA fraqgments ends, recurrent cfDNA fragment start sites, cfDNA coverage and cfDNA fragment size were compared to publicly available data on cfDNA methylation and gene expression from myeloid cells. We discovered that the ends of cfDNA fragments, particularly those containing CGs or CCGs, displayed a distinct pattern of enrichment or depletion, respectively, at methylated CpG positions throughout the genome. This phenomenon is consistent with structural models suggesting an increased interaction of CG fragment ends with nucleosomes. cfDNA fragments were more prevalent (up to 3.7 fold) and of larger sizes (up to 4-5 base larger) when derived from regions of methylated CpGs or transcriptional start sites of genes that were not actively expressed. Differences in cfDNA fragmentation reflected specific biological pathways associated with their tissue of origin (like E2f transcription factors and blood cell metabolism genes in cfDNA from healthy individuals). Through analyses of cfDNA from patients with cancer, we identified a connection between tumor-related hypomethylation, increased gene expression, and a global reduction in cfDNA fragment size. This connection may offer an explanation for the generally smaller cfDNA fragments found in individuals with cancer. We found that cancer-specific methylation at CpG sites from pancreatic cancers were associated with widespread changes in cfDNA fragment ends, particularly for patients with pancreatic (test statistic = Welch two sample t-test; p&amp;lt;2.2e-16) and other cancers. These findings establish a direct link between epigenetic modifications and cfDNA fragmentation that may have implications for non-invasive detection of cancer. Citation Format: Michaël Noë, Akshaya V. Annapragada, Zachariah H. Foda, Jamie E. Medina, Dimitrios Mathios, Stephen Cristiano, Christopher Cherry, Daniel C. Bruhm, Noushin Niknafs, Vilmos Adleff, Leonardo Ferreira, Hari Easwaran, Stephen Baylin, Jillian Phallen, Robert B. Scharpf, Victor E. Velculescu. DNA methylation and gene expression as determinants of genome-wide cell-free DNA fragmentation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 974.

Prognostic Role of Preoperative Chemotherapy in Liver-Limited Metastasis from Gastric Cancer.

We investigated the prognostic role of preoperative chemotherapy in patients who underwent hepatectomy for liver-limited metastasis (LLM) from gastric cancer (GC). A retrospective analysis was conducted for 52 consecutive patients who underwent macroscopically complete (R0 or R1) resection for synchronous or metachronous LLM from GC. Of the 52 patients, 18 (35%) received preoperative chemotherapy (PC group), while 34 (65%) underwent upfront surgery (US group). The PC group had a significantly longer overall survival than the US group (cumulative 5-year OS rate: 47.6% vs. 24.8%, p = 0.041). Multivariate analysis of OS revealed that preoperative chemotherapy was an independent favorable prognostic factor (hazard ratio: 0.445, p = 0.036). Patients showing a partial response to preoperative chemotherapy on RECIST had an improved OS compared with those exhibiting stable or progressive disease after preoperative chemotherapy and with US (p = 0.025), even among those with solitary LLM (p = 0.062) and multiple LLM (p = 0.026). At recurrence after hepatectomy for LLM, the PC group had a significantly higher incidence of solitary tumors than the US group (p = 0.043) and had a higher chance to undergo surgical resection for recurrent sites (p = 0.006). Preoperative chemotherapy can be recommended for patients with LLM from GC. The evaluation of the efficacy of preoperative chemotherapy offers additional information to determine the surgical indication for LLM.

Trends Over Time in Recurrence Patterns and Survival Outcomes after Neoadjuvant Therapy and Surgery for Pancreatic Cancer.

We aimed to determine if advances in neoadjuvant therapy affected recurrence patterns and survival outcomes after pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). Data are limited on how modern multimodality therapy affects PDAC recurrence and post-recurrence survival. Patients who received neoadjuvant therapy followed by curative-intent pancreatectomy for PDAC during 1998-2018 were identified. Treatments, recurrence sites and timing, and survival were compared between patients who completed neoadjuvant therapy and pancreatectomy in 1998-2004, 2005-2011, and 2012-2018. The study included 727 patients (203, 251, and 273 in the 1998-2004, 2005-2011, and 2012-2018 cohorts, respectively). Use of neoadjuvant induction chemotherapy increased over time, and regimens changed over time, with >80% of patients treated in 2012-2018 receiving FOLFIRINOX or gemcitabine with nab-paclitaxel. Overall, recurrence sites and incidence (67.5%, 66.1%, and 65.9%) remained stable, and 85% of recurrences occurred within 2 years of surgery. However, compared to earlier cohorts, the 2012-2018 cohort had lower conditional risk of recurrence in postoperative year 1 and higher risk in postoperative year 2. Overall survival increased over time (median, 30.6, 33.6, and 48.7mo, P < 0.005), driven by improved post-recurrence overall survival (median, 7.8, 12.5, and 12.6mo; 3-year rate, 7%, 10%, and 20%; P < 0.005). We observed changes in neoadjuvant therapy regimens over time and an associated shift in the conditional risk of recurrence from postoperative year 1 to postoperative year 2, although recurrence remained common. Overall survival and post-recurrence survival remarkably improved over time, reflecting improved multimodality regimens for recurrent disease.

Accurate location describe and management of lymph node recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma：a retrospective cohort study.

Describe the accurate locations of lymph node recurrence LNR of Chinese patients with postoperative thoracic esophageal squamous cell carcinoma (ESCC) is essential for determining the need for further surveillance protocols and treatments. We aimed to evaluate the patterns of postoperative ESCC and its current risk stratification with LNR. This population-based cohort study included a retrospective review of the medical records and image material of patients with ESCC who underwent LNR after radical surgery between January 2013 and September 2022, with a median follow-up time of 5.71 years. Clinical features were extracted from these records, and survival analysis was performed. The primary endpoint was the accurate location and range of LNR according to the nomenclature of the Japanese Society for Esophageal Diseases. The second endpoints was to explore the related factors of recurrence range (RR) and overall survival (OS) . A total of 3268 lymph node regions were recurrence from 1129 patients, with a mean of 2.89 regions per patient. No.104, 106 and 107 was the most common recurrence of thoracic ESCC with an LNR rate higher than 15%. In upper thoracic ESCC, No.105 was a common recurrence site and abdominal lymph node recurrence was rare. In lower thoracic ESCC, retroperitoneal lymph node was a unique regions (15.4%). Anastomotic recurrence is an important recurrence pattern in patients with postoperative esophageal cancer, with an incidence of 24.5%. Rates of lymph node recurrence in range of lymph node dissection was low (13.9%). The median time of LRT was 20.0 (1.5-184.0) months. High range of recurrence was associated with significantly poorer OS in patients. Multiple linear regression analysis identified demonstrated N stage, tumor differentiation, adjuvant radiotherapy and total lymph nodes removed were association with recurrence range for patients. Supraclavicular and upper mediastinums lymph nodes were common recurrence site for ESCC patients , and careful initial staging and surveillance are needed. Thorough lymph node dissection may reduce the range of regional recurrence.

Spatial Pattern of Intraprostatic Recurrence after Definitive External-Beam Radiation Therapy for Prostate Cancer: Implications for Focal Boost to Intraprostatic Dominant Lesion

Background/PurposeWe retrospectively investigated spatial pattern associations between primary and recurrent tumor sites following definitive external-beam radiation therapy (EBRT) for prostate cancer, using positron emission tomography/computed tomography (PET/CT) with a prostate-specific membrane antigen (PSMA)-targeted probe, 18F-FSU-880. MethodsAmong the patients who received PET/CT with 18F-FSU-880 in a phase 2 trial, which evaluated the tumor detection efficacy of PSMA-PET/CT for recurrent prostate cancer, patients with local intra-prostatic recurrence detected by PSMA-PET/CT following definitive EBRT were retrospectively analyzed. The prostate and seminal vesicles were divided into 14 sections in total. Two diagnostic radiologists separately re-evaluated the intra-prostatic location of the primary tumor on magnetic-resonance imaging and that of the recurrent tumor on PSMA-PET/CT, respectively, and the rate of overlap between primary and recurrent tumors was calculated. The overlap rate was defined as “the number of sections which overlapped between the primary tumor and recurrent tumor” divided by “the total number of sections of recurrent tumor”. A recurrent tumor was considered to be at the same location with an overlap rate equal to or greater than 75%, and a partial overlap was defined as an overlap rate between 25 and 74%. ResultsTwelve patients had local recurrence detected by PSMA-PET/CT. The median time to the diagnosis of local recurrence was 9.1 (range: 2.2–12.3) years after definitive EBRT.The recurrent tumor was detected at the same location in 25.0%, and a partial overlap was noted in 41.7%. ConclusionsLocal intra-prostatic recurrence after definitive EBRT often occurs at the same site or at a partially overlapping site adjacent to the primary IPDL. Our results support the merit of focal dose-escalation for intra-prostatic dominant lesions in definitive EBRT.

Patient-reported outcomes in inguinal hernia surgery-Results from the GENESIS study: A multinational multicenter study.

Chronic groin pain following inguinal hernia repair can be troublesome. The current literature is limited, especially from Asia and Africa. We aimed to evaluate patient-reported outcomes using the Carolinas Comfort Scale (CCS) following inguinal hernia repair at an international level, especially to include patients from Asia and Africa. An international cohort of surgeons was invited to collaborate and collect data of consecutive adult patients who underwent inguinal hernia repair. The data were collected to allow at least 2years of follow-up. A total score for CCS was calculated and compared for the following groups-patient age <30years versus (vs.)>30years; open versus laparoscopic repair, emergency versus elective surgery, and unilateral versus bilateral hernia repair. The CCS scores between Asia, Africa, and Europe were also compared. The mean total CCS score of patients operated in Asia (n=891), Europe (n=853), and Africa (n=157) were 7.32, 14.6, and 19.79, respectively. The total CCS score was significantly higher following open repair, emergency repair, and unilateral repair, with surgical site infections (SSI) and recurrence. In the subgroup analysis, the patients who underwent elective open repair in Europe had higher CCS scores than those in Asia. About 15% of patients had a CCS score of more than 25 after a minimum follow-up of 2years. The factors that influence CCS scores are indication, approach, complications, and geographic location.

The Correlation of Body Mass Index with Risk of Recurrence in Post-Menopausal Women with Breast Cancer Undergoing Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Background: The aim of this study was to investigate whether high body mass index (BMI) increases the risk of recurrence and correlates with higher glucose uptake in recurrent lesions in post-menopausal female patients with breast cancer. Methods: A hospital database was searched to retrieve breast cancer patients who had undergone an [18F]FDG PET/CT scan before neoadjuvant chemotherapy and curative-intent surgery. BMI was calculated at the baseline [18F]FDG PET/CT scan. There was a median follow-up of 5 years after the baseline PET/CT scan to identify recurrence in the breast (T_rec); lymph nodes (N_rec); and distant locations (M_rec). Furthermore, SUVmax was measured at the sites of recurrence. A chi-square test was used to investigate any difference in the frequency of any recurrence, T_rec, N_rec, and M_rec, between overweight women (BMI ≥ 25 kg/m2) and women with a BMI < 25 kg/m2 (p < 0.05). SUVmax was compared using a t-test (p < 0.05) between the two groups. Results: A total of 142 post-menopausal patients (BMI: 26.84 ± 5.59; 84 overweight and 58 with normal weight) were retrieved from the database. There were 48 recurrences at the follow-up. The chi-square test demonstrated in overweight women an increased frequency of any recurrence (35 vs. 13; p = 0.025) and T_rec (15 vs. 2; p = 0.018) and a higher T_rec SUVmax (4.74 ± 2.90 vs. 1.85 ± 0.63; p = 0.09) compared to women with a BMI < 25 kg/m2. Conclusions: BMI seems to correlate with an increased rate of recurrence, especially in the breast, and a higher glucose uptake in post-menopausal patients with recurrent breast cancer.

Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study).

No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.

Upfront surgery for stage IIIA/B non-small cell lung cancer: retrospective cohort study.

Stage III non-small cell lung cancer is a heterogeneous disease. Several international guidelines recommend neoadjuvant treatment before surgery; however, upfront surgery is the preferred approach for technically resectable non-small cell lung cancer in East Asia. The aim of this retrospective study was to evaluate the long-term outcomes of curative-intent upfront surgery in stage IIIA/B non-small cell lung cancer. Patients who underwent curative-intent upfront surgery with stage cIIIA/B non-small cell lung cancer were identified. The clinical and pathological variables and survival outcomes were evaluated. Overall, 664 patients were identified, of whom 320 (48.8%) had N2 disease, 66.7% were males, 49.4% had a smoking history, and 61.2% had lung adenocarcinoma. Lobectomy was the most performed surgical procedure (84.9%). A total of 40 patients (6.02%) had positive margins (R1/R2). The grade III adverse event rate was 2.0% (13 of 664). The median follow-up was 30.6 (range 1.9-97.7) months. At follow-up, the mortality rate was 13.3% (88 of 664) and 37.2% of patients (247 of 664) had recurrence. Lung (101 of 247 (40.9%)) and brain (53 of 247 (21.5%)) were the most common sites of recurrence. The median overall survival was 60.0 (95% c.i. 51.5 to 67.6) months, with overall survival probability at 1, 2, 3, and 5 years being 89.6%, 77.8%, 67.2%, and 49.0% respectively. The R0 cohort showed an improved median overall survival compared with the R1/R2 cohort (67.4 versus 26.5 months respectively; P = greater than 0.001). The multivariable analysis revealed that age greater than or equal to 65 years (HR 1.51, 95% c.i. 1.08 to 2.12; reference = age less than 65 years), tumour size (greater than or equal to 5 cm (HR 2.13, 95% c.i. 1.41 to 3.21) and greater than or equal to 3 cm but less than 5 cm (HR 1.15, 95% c.i. 0.78 to 1.71); reference = less than 3 cm), and adjuvant treatment (chemotherapy (HR 0.69, 95% c.i. 0.49 to 0.96) and targeted therapy (HR 0.30, 95% c.i. 0.12 to 0.76); reference = none) significantly predicted overall survival. Upfront surgery is an option for the management of stage IIIA/B non-small cell lung cancer.

Salvage endoscopic resection for perforation site recurrence of colonic polyp

Video 1Salvage endoscopic resection for perforation site recurrence.