Patterns Of Disease Recurrence Research Articles

A Single-Center Experience in Combined Oncological–Surgical Treatment for Resectable Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Non-small cell lung cancer (NSCLC) is the most common pulmonary malignancy, frequently diagnosed at an advanced stage (III/IV). Patients in the Locally Advanced Stage Subgroup (IIIA) are relatively few, yet compose heterogenic phenotypes, posing a diagnostic and treating challenge, leading to a lack of clinical guidelines regarding the optimal standard of care. Several approaches exist, with a general agreement that a combined oncological and surgical modality approach is required. In this current retrospective descriptive study, patients with operable stage IIIA NSCLC who underwent surgery between 2013 and 2020 were evaluated on several aspects, including the initial diagnosis, neoadjuvant regimens, outcomes of surgical intervention, and overall survival at 2 years and 5 years following treatment. A total of 35 patients had neoadjuvant oncological treatment (mostly chemoradiation therapy) prior to surgery, out of which 28 patients were diagnosed with stage IIIA NSCLC. In post-operative assessment of pathological staging, downstaging was reported in 19 patients, of which 25% of cases were defined as a complete pathological response. The 2-year overall survival rate was 65% and the 5-year overall survival rate was 62%. The main pattern of disease recurrence was distant metastasis.

Patterns of recurrence in HNSCC patients treated definitively with upfront surgery, chemoradiation.

Locally-advanced oropharynx (LA-OPSCC) and hypopharynx/larynx (LA-HPLSCC) cancers may be treated with surgical or non-surgical modalities. While survival outcomes are comparable, patterns of disease recurrence are not well established. Retrospective review of 98 consecutive patients with LA-OPSCC or LA-HPLSCC treated by either surgery plus adjuvant therapy (S-POAT, n = 48) or chemoradiation (CRT, n = 50). CRT-treated patients had higher recurrence risk (42% vs 14.6%, p = 0.003). This was significant only among LA-OPSCC (p = 0.002) but not LA-HPLSCC patients (p = 0.159). Median time to recurrence in LA-OPSCC was 16.8 vs 11.6 months, and 16.6 vs 15.1 months in LA-HPLSCC, comparing surgically treated and CRT cohorts. Surgically-treated p16-negative LA-OPSCC experienced improved locoregional control than CRT-treated patients (100% vs 12.5%, p = 0.045) and 3-year RFS (83.0% vs 33.3%, p < 0.001). Locoregional control and RFS benefit was observed in surgically treated p16 negative LA-OPSCC patients. Locoregional recurrence is the main reason of treatment failure in LA-HNSCC, occurring commonly within the first 2 years post-treatment, regardless of treatment option.

The Clinical Behavior and Recurrence Patterns of Oral Cavity Cancer in Oral Lichen Planus Patients.

Oral lichen planus (OLP) is a chronic inflammatory disorder involving epithelia with squamous differentiation. Although described as a potential malignant precursor, the characteristics of malignancies arising among these patients are not widely described. Our goal was to describe the patterns of disease recurrence of patients with oral cavity squamous cell carcinoma (OSCC) arising on the background of OLP. A retrospective analysis of all surgically treated patients with OSCC at a university-affiliated tertiary care center between 2000 and 2020. Two hundred seventy-nine patients with OSCC treated surgically were included. Forty (14.3%) had OLP. The mean age of patients with OLP was 70.9 years compared with 64.3 years for non-OLP patients (p = 0.03). OLP patients had a significantly higher rate of disease recurrence, persistence, or multiple primary disease (70% vs. 33.9%, p < 0.001). The mean number of sequential oncologic events for each patient with recurrence was also significantly higher among OLP patients (1.86 vs. 1.36, p = 0.03), a difference explained by a higher rate of multiple primary presentations (0.71 vs. 0.28, p = 0.008). A significant difference in disease-free survival (DFS) was demonstrated between the groups as patients with OLP had a lower 5-year DFS (34.7% vs. 61.3%, log-rank p value <0.001). On multivariate analysis, OLP was significantly associated with multiple primary events (p < 0.001, Odds ratio = 7.42, 95% confidence interval 2.9-19). OSCC patients with OLP background demand close clinical follow-up, as multiple primary disease is significantly more common and the DFS is significantly lower among these patients. A thorough clinical evaluation for all oral cavity subsites is mandatory. 3 Laryngoscope, 2024.

Benefit, recurrence pattern, and toxicity to adjuvant anti-PD-1 monotherapy varies by ethnicity and melanoma subtype: An international multicenter cohort study

Anti-Program-Death-1 (PD-1) is a standard adjuvant therapy for patients with resected melanoma. We hypothesized that there are discrepancies in survival, recurrence pattern and toxicity to adjuvant PD-1 between different ethnicities and melanoma subtypes. We performed a multicenter cohort study incorporating 6 independent institutions in Australia, China, Japan, and the United States. The primary outcomes were recurrence free survival (RFS) and overall survival (OS). Secondary outcomes were disease recurrence patterns and toxicities. In total 534 patients were included. East-Asian/Hispanic/African reported significantly poorer RFS/OS. Nonacral cutaneous or melanoma of unknown primary reported the best RFS/OS, followed by acral, and mucosal was the poorest. Within the nonacral cutaneous or melanoma of unknown primary subtypes, East-Asian/Hispanic/African reported significantly poorer RFS/OS than Caucasian. In the multivariate analysis incorporating ethnicity/melanoma-subtype/age/sex/stage/lactate dehydrogenase/BRAF (v-Raf murine sarcoma viral oncogene homolog B)-mutation/adjuvant radiotherapy, East-Asian/Hispanic/African had independently significantly poorer outcomes (RFS: HR, 1.71; 95% CI, 1.19-2.44 and OS: HR, 2.34; 95% CI, 1.39-3.95), as was mucosal subtype (RFS: HR, 3.25; 95% CI, 2.04-5.17 and OS: HR, 3.20; 95% CI, 1.68-6.08). Mucosal melanoma was an independent risk factor for distant metastasis, especially liver metastasis. East-Asian/Hispanic/African had significantly lower incidence of gastrointestinal/musculoskeletal/respiratory/other-rare-type-toxicities; but higher incidences of liver toxicities. A retrospective study. Ethnicity and melanoma subtype are associated with survival and recurrence pattern in melanoma patients treated with adjuvant anti-PD-1. Toxicity profile differs by ethnicity and may require a precision toxicity surveillance strategy.

Pembrolizumab versus methotrexate, docetaxel, or cetuximab in recurrent or metastatic head and neck squamous cell carcinoma (KEYNOTE-040): Subgroup analysis by pattern of disease recurrence

BackgroundIn the phase 3 KEYNOTE-040 study, pembrolizumab prolonged OS versus chemotherapy in previously treated recurrent or metastatic (R/M) HNSCC. We present a post hoc subgroup analysis by disease recurrence pattern: recurrent-only, recurrent and metastatic (recurrent-metastatic), and metastatic-only HNSCC. Materials and MethodsPatients had HNSCC that progressed during or after platinum-containing treatment for R/M disease or had recurrence or progression within 3–6 months of previous platinum-containing definitive therapy for locally advanced disease. Patients were randomly assigned (1:1) to pembrolizumab 200 mg Q3W or investigator’s choice of standards of care (SOC): methotrexate, docetaxel, or cetuximab. Outcomes included OS, PFS, ORR, and DOR. The data cutoff was May 15, 2017. ResultsThere were 125 patients (pembrolizumab, 53; SOC, 72) in the recurrent-only subgroup, 204 in the recurrent-metastatic subgroup (pembrolizumab, 108; SOC, 96), and 166 in the metastatic-only subgroup (pembrolizumab, 86; SOC, 80). The hazard ratio (95% CI) for death for pembrolizumab versus SOC was 0.83 (0.55–1.25) in the recurrent-only, 0.78 (0.58–1.06) in the recurrent-metastatic, and 0.74 (0.52–1.05) in the metastatic-only subgroups. PFS was similar between treatment arms in all subgroups. ORR was 22.6% for pembrolizumab versus 16.7% for SOC in the recurrent-only, 10.2% versus 6.3% in the recurrent-metastatic, and 15.1% versus 8.8% in the metastatic-only subgroups. DOR was numerically longer with pembrolizumab in all subgroups. ConclusionPembrolizumab provided numerically longer OS and durable responses in all subgroups compared with SOC, suggesting that patients with previously treated R/M HNSCC benefit from pembrolizumab regardless of recurrence pattern.

Management of Medullary Thyroid Cancer: Patterns of Recurrence and Outcomes of Reoperative Surgery.

There remains uncertainty regarding the optimal extent of initial surgery and management of recurrent disease in medullary thyroid cancer (MTC). We aim to describe the patterns of disease recurrence and outcomes of the reoperative surgery in a cohort of consecutively treated patients at a specialized tertiary referral center. A retrospective cohort study of 235 surgically treated patients with MTC at a tertiary referral center was performed using prospectively collected data. In the study period 1986-2022, 235 patients underwent surgery for MTC. Of these, 45 (19%) patients had reoperative surgery for cervical nodal recurrence at a median (range) 2.1 (0.3-16) years following the index procedure. After a median follow-up of 4 years, 38 (84%) patients remain free of structural cervical recurrence, although 15 (33%) underwent 2 or more reoperative procedures. No long-term complications occurred after reoperative surgery. Local cervical recurrence was independently predicted by pathologically involved nodal status (OR 5.10, P = .01) and failure to achieve biochemical cure (OR 5.0, P = .009). Local recurrence did not adversely affect overall survival and was not associated with distant recurrence (HR 0.93, P = .83). Overall survival was independently predicted by high pathological grade (HR 10.0, P = .002) and the presence of metastatic disease at presentation (HR 8.27, P = 0018). Loco-regional recurrence in MTC does not impact overall survival, or the development of metastatic disease, demonstrating the safety of the staged approach to the clinically node-negative lateral neck. When recurrent disease is technically resectable, reoperative surgery can be undertaken with minimal morbidity in a specialized center and facilitates structural disease control.

The existence of biliary intraepithelial neoplasia at resection margin is not a risk factor for recurrence of biliary tract cancer

Abstract Background Invasive carcinoma or dysplasia (biliary intraepithelial neoplasia [BilIN]) is often found in the surgical stumps of biliary tract cancer. We investigated whether the presence of BilIN at the surgical margin is a risk factor for recurrence. Materials and Methods Seventy-five consecutive patients who underwent curative resection for biliary tract cancer were included in this study. We retrospectively evaluated the surgical margin status (negative, BilIN, or positive) and analyzed the postoperative disease recurrence rate and recurrence pattern by the status. Results The disease-free survival rate was significantly worse in the positive margin group than in the negative margin group (11 vs 18 months, P = 0.027). There were no statistical differences between the BilIN-positive group and the other two groups. In the multivariate analysis, infiltrative growth c (hazard ratio [HR], 3.348; 95% confidence interval [CI], 1.368–8.195; P = 0.008) and pathological exhumed margin (HR, 2.670; 95% CI, 1.097–6.495; P = 0.030) were independent recurrence factors. The margin status of BilIN was not associated with recurrence (HR, 0.867; 95% CI, 0.491–2.946; P = 0.687). Conclusions The BilIN component at the surgical margin was not associated with short-term recurrence, but the pathological exhumed margin positive and infiltrative growth c were. Infiltrative growth c may be a potential predictive factor for recurrence.

Patterns of recurrent disease after neoadjuvant chemoradiotherapy and esophageal cancer surgery with curative intent in a tertiary referral center

BackgroundRecurrence is frequently observed after esophageal cancer surgery, with dismal post-recurrence survival. Neoadjuvant chemoradiotherapy followed by esophagectomy is the gold standard for resectable esophageal tumors in the Netherlands. This study investigated the recurrence patterns and survival after multimodal therapy. MethodsThis retrospective cohort study included patients with recurrent disease after neoadjuvant chemoradiotherapy followed by esophagectomy for an esophageal adenocarcinoma in the Amsterdam UMC between 01 and 01–2010 and 31-12-2018. Post-recurrence treatment and survival of patients were investigated and grouped by recurrence site (loco-regional, distant, or combined loco-regional and distant). ResultsIn total, 278 of 618 patients (45.0%) developed recurrent disease after a median of 49 weeks. Thirty-one patients had loco-regional (11.2%), 145 distant (52.2%), and 101 combined loco-regional and distant recurrences (36.3%). Post-recurrence survival was superior for patients with loco-regional recurrences (33 weeks, 95%CI 7.3–58.7) compared to distant (12 weeks, 95%CI 6.9–17.1) or combined loco-regional and distant recurrent disease (18 weeks, 95%CI 9.3–26.7). Patients with loco-regional recurrences treated with curative intent had the longest survival (87 weeks, 95%CI 6.9–167.4). ConclusionRecurrent disease after potentially curative treatment for esophageal cancer was most frequently located distantly, with dismal prognosis. A subgroup of patients with loco-regional recurrence was treated with curative intent and had prolonged survival. These patients may benefit from intensive surveillance protocols, and more research is needed to identify these patients.

Patterns of recurrent disease after neoadjuvant chemoradiotherapy and esophageal cancer surgery with curative intent in a tertiary referral center

Patterns of recurrent disease after neoadjuvant chemoradiotherapy and esophageal cancer surgery with curative intent in a tertiary referral center

Effect of resection margin status on recurrence pattern and survival in distal pancreatectomy for left-sided pancreatic ductal adenocarcinoma.

675 Background: The association of resection margin status with recurrence and survival after pancreatectomy for pancreas ductal adenocarcinoma (PDAC) remains controversial. The aim of this study was to identify the effect of R1 resection on recurrence pattern and survival after distal pancreatectomy for left-sided PDAC. Methods: Patients who underwent distal pancreatectomy for PDAC at two high-volume institutions between January 2010 and December 2017 were retrospectively reviewed. Perioperative characteristics, pathological outcomes, recurrence pattern and survival data were collected to compare R0 resection and R1 resection. Results: Among 558 patients who underwent distal pancreatectomy for PDAC, 158 patients (28.3%) showed R1 resection margin. R1 patients were associated with large tumor size (3.3 cm vs. 3.7 cm, p= 0.006) and lower number of positive lymph nodes (1.3 vs. 2.0, p= 0.001). Median overall survival (37.3 months vs. 20.1 months, p&lt; 0.001) and recurrence-free survival (14.6 months vs. 6.9 months, p&lt; 0.001) significantly differed between the R0 and R1 groups. Disease recurrence patterns were not statistically different between the two groups ( p = 0.182). Among the recurrence patterns, peritoneal carcinomatosis had the shortest recurrence-free survival (5.6 months, p &lt; 0.05) and overall survival (13.6 months, p &lt; 0.05) compared with all other recurrence patterns. Conclusions: R1 resection margin after distal pancreatectomy was associated with poor survival and early recurrence. There is no significant difference in recurrence pattern between R0 and R1. Among the recurrence patterns, peritoneal carcinomatosis showed the worst prognosis.

Patterns and Timing of Recurrence following CRS and HIPEC in Colorectal Cancer Peritoneal Metastasis.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) is an established treatment of Colorectal Peritoneal Metastases (CRPM). This study aims to determine the timing and patterns of recurrent disease on imaging following complete CRS/HIPEC. Retrospective analysis of a national peritoneal tumour service database identified CRPM patients with complete CRS/HIPEC(CC0) from 2005 to-2018. Patients with<2 years follow-up or and those where post-operative histology from the CRS/HIPEC procedure did not confirm CRPM from their original colorectal cancer were excluded. Time to recurrence was measured from surgery to first radiologically illustrated recurrence. CT was the primary modality used, supplemented by PET-CT or MRI if required. Outcomes of interest were survival data (including overall survival (OS), disease-free survival (DFS) and peritoneal-recurrence free survival (PRFS)), timing and patterns of recurrent disease. 146 of the 176 patients identified were eligible for inclusion. Median OS for all study patients was 45.2 months (95% CI 38-53 months), median DFS was 11.7 months (95% CI 9-14 months), and median PRFS was 25.2 months (95% CI 14.7-30 months). Recurrent disease was seen in 112 cases (77%), radiologically classified as intraperitoneal in 50 patients (44%), single site systemic in 21 patients (19%) and multi-site in 41 patients (37%). CT detection rate for disease recurrence was 88%. Subgroup analyses showed that PCI ≥12, positive nodal primary disease and synchronous peritoneal disease were associated with worse outcomes. Patients selected for CRS/HIPEC for CRPM have an OS>45 months, with the majority recurring systemically within a year. Peritoneal recurrence is a later event after several years. Surveillance programs in this group should be most intensive in the first 2 years after surgery, using CT with oral and intravenous contrast.

The infrequent large pelvi-perineal tumors as a surgical dilemma: en bloc resection and long-term results

To assess long-term results of surgical resections of the sporadic extra-large pelvi-perineal soft tissue tumors, a retrospective series of patients referred to the National Cancer Institute 2001–2022 (tertiary care cancer university hospital in Egypt) was designed. Thirteen patients (3 males) averaged age 57 years had large 29 cm (18–38) pelvi-perineal tumors (10 to the paraanal ischiorectal spaces and 3 to the vulva) plus upper intra-abdominal extensions in 9 patients (69%). Symptoms were nonspecific with delayed presentation that averaged 22-month. The entire underwent combined open abdomino-perineal approach to widely en masse resect tumors plus infiltrated organs. No downsizing hormonal treatment was offered preoperative. Main outcome measures were disease free survival, recurrence pattern and salvage. Extensive pelvic and perineal tumor resection is tough and meticulous but straightforward with minor (Clavien-Dindo Classification (CDC) grade I &amp; II) early and delayed morbidity. Resection extends to hysterectomy, vaginectomy and vascular resection. Histopathology plus immunohistochemistry showed 9-aggressive angiomyxoid tumors (AA), 2-fibromatosis and 2-neurofibromas (NF). Margins of resection are all adequate (R0) except for 2 (Resection margin 1 (R1)). After 50-month median follow up, 8/13 total series (61.5%) were surviving free of disease. 4/9 of AA (44%) had local perineal and/or pelvic recurrences (13–37 months) and all were amenable to curative salvage resections; while, 1/2 patients with fibromatosis died of disseminated peritoneal relapses. No systemic metastases are noticed. Extensive tumors meticulous surgery with experienced pelvic dissection and resection could offer alone long term cure even after recurrences with minor morbidity in a good percent. Fertility sparing resection is not oncologically safe because of the frequent uterine and ovarian invasions.

Patterns of failure in pediatric medulloblastoma and implications for hippocampal sparing.

Hippocampal avoidance (HA) has been shown to preserve cognitive function in adult patients with cancer treated with whole-brain radiation therapy for brain metastases. However, the feasibility of HA in pediatric patients with brain tumors has not been explored because of concerns of increased risk of relapse in the peri-hippocampal region. Our aim was to determine patterns of recurrence and incidence of peri-hippocampal relapse in pediatric patients with medulloblastoma (MB). We identified pediatric patients with MB treated with protons between 2002 and 2016 and who had recurrent disease. To estimate the risk of peri-hippocampal recurrence, three hippocampal zones (HZs) were delineated corresponding to ≤5 mm (HZ-1), 6 to 10 mm (HZ-2), and >10mm (HZ-3) distance of the recurrence from the contoured hippocampi. To determine the feasibility of HA, three standard-risk patients with MB were planned using either volumetric-modulated arc therapy (VMAT) or intensity-modulated proton therapy (IMPT) plans. Thirty-eight patients developed a recurrence at a median of 1.6years. Of the 25 patients who had magnetic resonance imaging of the recurrence, no patients failed within the hippocampus and only two patients failed within HZ-1. The crude incidence of peri-hippocampal failure was 8%. Both HA-VMAT and HA-IMPT plans were associated with significantly reduced mean dose to the hippocampi (p<.05). HA-VMAT and HA-IMPT plans were associated with decreased percentage of the third and lateral ventricles receiving the prescription craniospinal dose of 23.4Gy. Peri-hippocampal failures are uncommon in pediatric patients with MB. Hippocampal avoidance should be evaluated in a prospective cohort of pediatric patients with MB. In this study, the patterns of disease recurrence in patients with a pediatric brain tumor known as medulloblastoma treated with proton radiotherapy were examined. The majority of failures occur outside of an important structure related to memory formation called the hippocampus. Hippocampal sparing radiation plans using proton radiotherapy were generated and showed that dose to the hippocampus was able to be significantly reduced. The study provides the rationale to explore hippocampal sparing in pediatric medulloblastoma in a prospective clinical trial.

Recurrence Patterns for Regionally Metastatic Melanoma Treated in the Era of Adjuvant Therapy: A Systematic Review and Meta-Analysis.

The purpose of this systematic review was to examine the timing and patterns of recurrence for patients with regionally metastatic melanoma on the basis of nodal management and receipt of adjuvant therapy. We identified randomized controlled trials and non-randomized studies published between 2010 and 2020 that reported timing and/or patterns of recurrence. We evaluated recurrence-free survival (RFS), location of recurrence, and surveillance strategy on the basis of receipt of adjuvant systemic therapy and nodal management with observation versus completion dissection. We compared differences in patterns of recurrence across studies using RevMan. RFS was evaluated graphically using point estimates and confidence intervals. Among the 19 publications, there was wide variation in study populations, imaging surveillance regimens, and format of recurrence reporting. Patterns of disease recurrence did not differ between adjuvant and placebo/observation groups. A total of 11 studies reported RFS at variable time intervals, which ranged in adjuvant therapy groups (38-88% at 1 year, 29-67% at 2 years, 33-58% at 3 years, and 34-53% at 5 years) and placebo/observation groups (47-63% at 1 year, 39-47% at 2 years, 33-68% at 3 years, and 57% at 5 years). Anti-PD-1 immune therapy and BRAF/MEK inhibitor therapy were superior to placebo at year 1. We found that adjuvant treatment improved RFS but did not alter the patterns of disease recurrence compared with patients managed without adjuvant systemic treatment. Future studies should separately report sites of disease recurrence on the basis of specific adjuvant systemic treatment and surveillance practices to better advise patients about their patterns and risk of recurrence.

Effect of resection margin status on recurrence pattern and survival in distal pancreatectomy for left-sided pancreatic ductal adenocarcinoma.

The association of resection margin status with recurrence and survival after pancreatectomy for pancreas ductal adenocarcinoma (PDAC) remains controversial. The aim of this study was to identify the effect of R1 resection on recurrence pattern and survival after distal pancreatectomy for left-sided PDAC. Patients who underwent distal pancreatectomy for PDAC at two high-volume institutions between January 2010 and December 2017 were retrospectively reviewed. Perioperative characteristics, pathological outcomes, recurrence pattern, and survival data were collected to compare R0 resection and R1 resection. Among 558 patients who underwent distal pancreatectomy for PDAC, 158 patients (28.3%) showed R1 resection margin. R1 patients were associated with large tumor size (3.3cm vs. 3.7 cm, p=.006) and lower number of positive lymph nodes (1.3 vs. 2.0, p=.001). Median overall survival (37.3months vs. 20.1 months, p < .001) and recurrence-free survival (14.6months vs. 6.9 months, p < .001) significantly differed between the R0 and R1 groups. Disease recurrence patterns were not statistically different between the two groups (p=.182). Among the recurrence patterns, peritoneal carcinomatosis had the shortest recurrence-free survival (5.6months, p < .05) and overall survival (13.6months, p < .05) compared with all other recurrence patterns. R1 resection margin after distal pancreatectomy was associated with poor survival and early recurrence. There is no significant difference in recurrence pattern between R0 and R1. Among the recurrence patterns, peritoneal carcinomatosis showed the worst prognosis.

Long Non-coding RNA INE1 Induced Autophagy Promotes Sensitivity of Prostate Cancer Cells to Cisplatin

Prostate cancer is most prevalent malignancy of males in the world. In recent years, long non-coding RNAs (lncRNAs) were identified, and their functions are associated with prostate cancer initiation and progression. However, their molecular mechanisms still need to be elucidated before the clinical utility. In the present study, we identified the correlation of lncRNA inactivation escape 1 (INE1) with the characterization in prostate cancer patients, and detected the roles of INE1 in cell autophagy and apoptosis in prostate cancer cells. Our results showed that the lncRNA INE1 expression highly correlate with patients’ survival times, tumor stage, biochemical recurrence, disease recurrence and Gleason pattern. High expression of INE1 was detected in prostate cancer cells, and knockdown INE1 by siRNA resulted in significant inhibition of cell viability. In addition, silencing INE1 induced early autophagy and pro-apoptosis, which augments cisplatin (CDDP)-induced cell apoptosis. Moreover, INE1 played an anti-apoptotic role by targeting the serine/arginine-rich splicing factor 2 (SRSF2).

Prospective Evaluation of Interim FDG-PET Imaging during Chemoradiation for Anal SCC

<h3>Purpose/Objective(s)</h3> De-escalation of therapy for anal squamous cell carcinoma is under investigation in multiple prospective randomized trials. Imaging metrics from (F-18) fluorodeoxyglucose positron emission tomography (PET) before and during chemoradiation may serve as a biomarker to tailor treatment and aid in appropriate patient and dose selection. <h3>Materials/Methods</h3> From June 2012 to July 2021, 56 patients with anal canal cancer were enrolled in two prospective studies (30 and 26 patients, respectively) of PET prior to and during CRT after receiving ∼30 Gy. PET metrics of the primary site were calculated for the pre-treatment and interim images, including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) based on 40% SUVmax (MTV40, TLG40) or SUV 2.5 (MTV2.5, TLG2.5) thresholds. Associations between absolute pre-treatment and interim PET metrics and freedom from local/regional recurrence (FFLR) were investigated using the Cox proportional hazards method. Local/regional recurrence was defined as primary or nodal (in-field) recurrence. No adjustment was made for multiple comparisons. <h3>Results</h3> Forty-four patients were eligible for analysis. Patients with non-squamous cell histology (adenocarcinoma, melanoma) (3 patients), recurrent anal cancer (1 patient), metastatic disease (1 patient), and incomplete studies due to treatment toxicity or patient choice (7 patients) were excluded. Median follow-up was 2.4 years. Clinical stage was T3 or T4 in 43% of patients, and 52% were node positive. Seven patients have expired and disease recurrence patterns following treatment included local/regional (5 patients) and distant disease (7 patients). On univariate analysis, age, T and N stage, duration of treatment, and HIV status did not significantly correlate with FFLR. TLG2.5 (1.05 [0.99-1.11]) was marginally associated with FFLR. No pretreatment metrics or other interim metrics were significantly associated with FFLR. Multivariate analysis was not conducted given the small number of events (N=5). <h3>Conclusion</h3> In this expanded pilot study, characteristics of PET acquired during treatment of anal canal cancer were not significantly associated with FFLR. Given the limited number of FFLR events, definitive conclusions about the utility of interim PET cannot be drawn. The correlation of various PET metrics with FFLR warrants further investigation to determine if interim PET as an imaging biomarker can be used to personalize treatment, potentially in the setting of dose de-escalation.

Patterns of Recurrence and Progression for Unresectable Cholangiocarcinoma on Orthotopic Liver Transplant Protocol

<h3>Purpose/Objective(s)</h3> Neoadjuvant radiotherapy and chemotherapy (CHT) followed by orthotopic liver transplant (OLT) offers the highest chance of disease-free survival for patients with unresectable cholangiocarcinoma (CCA). The purpose of this study was to evaluate patterns of disease recurrence and progression in patients treated on OLT protocol. <h3>Materials/Methods</h3> Through retrospective chart review, we identified patients treated on institutional OLT protocol for unresectable intrahepatic or hilar CCA at a single academic institution from 2012-2019. Patients received SBRT to a total dose of 40 Gy in 5 fractions, delivered over 7-12 days followed by adjuvant CHT (gemcitabine/cisplatin, fluorouracil [5FU] or a capecitabine based regimen). Per protocol, restaging scans were obtained every 3 months until progression or OLT. <h3>Results</h3> Of 26 patients treated on protocol, nine underwent OLT (34.6%), of which six were male (66.7%), median age 51 (36-66), eight hilar tumors (88.9%), one intrahepatic (11.1%), and median size 2.85 cm (2.2-4.3). All patients were treated to 40 Gy in five fractions with a median PTV of 66.6 cc (30.4-202) and median time of 20.4 weeks (8.7-89.1) on adjuvant CHT. Median time from completion of SBRT to OLT was 61.4 weeks (26.6-97.6). Following OLT, four of nine (44.4%) achieved a pathologic complete response (ypT0) in the explanted liver, of which two patients developed recurrence (one at the porta hepatis, one in the lung). Five of nine OLT patients (55.6%) developed recurrent disease (three local, one local and distant, one distant) with median time to recurrence of 49.9 weeks (35.9-127.7) and median time to death of 124.0 weeks (39.3-200.9). Four patients remain in remission with median follow-up of 166.1 weeks (2.4-370.7). 17/26 patients did not proceed to OLT due to disease progression in 13 (10 local, 3 distant), with a median time to progression after SBRT of 37.0 weeks (3.7-81.4), death following recurrent cholangitis in three, and liver failure in one. Median OS for patients who underwent OLT versus those who did not was 172.2 (135.3-285.0) and 78.4 (26.1-219.6) weeks, respectively. <h3>Conclusion</h3> In this small group of patients with unresectable CCA treated with SBRT, CHT, and OLT, there were encouraging rates of pathologic complete response; however, a subset of patients will still develop disease recurrence. All patients who did not make it to OLT developed progression, illustrating a continued unmet need to improve therapeutic options for CCA.

Patterns of care for relapsed oesophageal cancer after initial curative trimodality therapy: Long-term follow-up of the SAKK 75/08 trial

BackgroundRecurrent oesophageal cancer after the initial curative multimodality treatment is a disease condition with a poor prognosis. There is limited evidence on recurrence patterns and on the optimal therapeutic approach. MethodsWe analysed the pattern of disease recurrence and subsequent therapies in patients with recurrent oesophageal cancer based on prospectively collected data within a predefined subproject of the randomised phase 3 trial Swiss Group for Clinical Cancer Research (SAKK) 75/08. ResultsAmong 300 patients included in the SAKK 75/08 trial, tumour recurrence was observed in 103 patients with a median follow-up of 5.8 years. Locoregional recurrence only was found in 26.2% of the patients, 21.4% of patients had both distant and locoregional recurrence and 52.4% of patients had distant recurrence only. Fifty-nine patients (58%) received at least one line of systemic therapy at recurrence, most commonly oxaliplatin-based combination therapies for adenocarcinoma and single-agent chemotherapy for squamous cell carcinoma. Local therapies, most commonly palliative radiotherapy, were used in 49 patients (48%). Six patients underwent a second curative resection or radiochemotherapy. We found no significant overall survival difference for isolated locoregional recurrence versus distant recurrence (15.1 versus 8.7 months, p = 0.167). In a multivariable Cox regression model, time from oesophagectomy to recurrence and the number of recurrence sites as well as the use of systemic therapy or a second curative local therapy significantly correlated with overall survival. ConclusionsRecurrent oesophageal cancer remains a disease with a poor prognosis and requires multidisciplinary management. A second curative approach for localised disease recurrence may be an option for highly selected patients.

1634P Patterns of disease recurrence in relation to the extent of lymph node sampling in patients with resected lung carcinoid: A population-based study

In patients (pts) with resected pulmonary carcinoids, recurrence of disease may occur up to 10 years after surgery, but the exact incidence remains unknown. Locoregional lymph node (LN) involvement predicts poor prognosis. We evaluated recurrence-free interval (RFI) patterns in relation to the extent of surgical LN sampling.