Common Site Research Articles

Oral Lymphangioma: An Original Series of Three Cases with Review

Lymphangiomas are benign hamartomatous tumors of lymphatic origin which results from sequestration of lymphhatic tissues that do not communicate with other lymphatic channels. They may occur with hemangiomas and have high predilections for head and neck region (50-70%). They may occur at birth (60-70%) or till two years of age (90%) and rarely in adults. The most common site of occurrence in the mouth is dorsum of tongue being followed by lips, buccal mucosa, soft palate and floor of mouth. Tongue lymphangioma may present as localized or diffused growth that may result in macroglossia, impaired speech and difficulty in mastication. There are different treatment options; surgical excision being the most effective mode of treatment. Here we have reported three different cases of oral lymphangiomas, two of which occurring in the tongue and one in the buccal mucosa.

Hydatid Cyst at Unusual Location (Spleen) - A Case Report

Echinococcosis or Hydatid disease is a zoonosis endemic in agricultural areas of the world. It is caused by tapeworm of genus Echinococcus excreted in the faeces of infected dogs. Most common site of involvement is liver (50-77%) followed by lungs (18-35%), abdominal cavity and brain. Splenic hydatid cyst is a rare entity constituting 0.5 - 4% of abdominal hydatid disease. We report a case of 62 yrs old female who presented with vague abdominal pain and vomiting. Her abdominal CECT revealed a cystic lesion with peripheral calcified foci at lower pole of spleen. All other investigations were normal except for raised serum echinococcus IgG levels. Splenectomy specimen was received and histopathological examination confirmed it as hydatid cyst. Microscopy showed outer acellular laminated membrane, inner germinal layer with scolices along with eosinophilic inflammatory infiltrate. Patients presenting with hydatid disease are usually asymptomatic or can have vague abdominal pain. The disease is associated with recurrences, fatal anaphylaxis if neglected and high morbidity and mortality, therefore it should be considered as a differential for any cystic mass found in any part of the body.

Comparison of Neurosensory Recovery of the Inferior Alveolar Nerve After Open and Closed Reduction for Mandibular Fractures: A Prospective Study.

Traumatic mandibular fractures are the most common fractures of the facial region and are associated with loss of neurosensation in the inferior alveolar nerve (IAN). The present study aimed to compare IAN recovery after traumatic mandibular fractures between the open and closed reduction methods. The study included 90 patients with traumatic mandibular fractures of the body, angle, and symphysis, divided into two groups of 45 patients: group 1 was treated with closed reduction and fixation with rich arch-bar fixation under local anesthesia, and group 2 was treated with open reductionand rigid internal fixation with 2-mm titanium mini plates and monocortical screws (6 mm), and the plate was fixed to the fractured bony fragments. All patients underwent neurosensory testing using the Zuniga and Essick algorithm at baseline (preoperative), one week after surgery (postoperative), at three months, and at six months of follow-up. No statistically significant differences were observed in IAN recovery between the groups. The most common site of fracture was the body (44% in group 1 and 56% in group 2). The maximum recovery was observed in the younger age group (25-30 years). At baseline, functional nerve recovery was observed in 40 cases (88%) in group 1 and 38 cases (84%) in group 2, and the difference was not statistically significant. Levels A and B tests were affected by surgical management and improved after three months.The total recovery in group 1 ranged from 60% to 80%, and that in group 2 ranged from 56% to 72%. Based on the findings of the current study, both methods are recommended for surgical management of traumatic mandibular fractures with IAN recovery in 60-80% of cases six months postoperatively.

Morel-Lavallée Lesion: A Case Report

The Morel-Lavallée lesion (MLL) is an uncommon, traumatic internal degloving injury of the soft tissues and the fascia. The MLLs are often misdiagnosed or delayed in being diagnosed due to the severity of other injuries from an accident. Sonography and/or magnetic resonance imaging may be used to confirm the diagnosis. After the MLL is diagnosed, treatment options vary from conservative options to surgical methods depending on the chronicity of the lesion. The case study presented occurs in the most common site for the injury, the hip and pelvis.

Bone Turnover Markers, n-Terminal Propeptide of Type I Procollagen and Tartrate-Resistant Acid Phosphatase Type 5b, for Predicting Castration Resistance in Prostate Cancer.

Bone is a common site of prostate cancer metastasis. Bone turnover markers n-terminal propeptide of type I procollagen (P1NP) and tartrate-resistant acid phosphatase type 5b (TRACP-5b) are highly sensitive to bone remodeling activity. However, their prognostic significance as markers of prostate cancer is unknown. This study retrospectively examined the usefulness of P1NP and TRACP-5b as prognostic biomarkers. Castration-resistant prostate cancer recurrence-free survival (CFS) was estimated using the Kaplan-Meier method. A predictive model for CFS was constructed using multivariate analysis. This study enrolled 255 patients diagnosed with prostate cancer at Kanazawa University Hospital. The median follow-up was 115.1 months. Patients with both high serum P1NP and TRACP-5b levels, defined as having a poor bone turnover category (BTC), had significantly shorter CFS. Multivariate analysis identified Gleason score, metastasis, and BTC poor as predictors for castration resistance in prostate cancer. Using these three factors, a prognostic model was established, categorizing patients into low-risk (no or one factor) and high-risk (two or three factors) groups. In the low-risk group, the median CFS was not reached, contrasting with 19.1 months in the high-risk group (hazard ratio, 32.23, p < 0.001). Combining P1NP and TRACP-5b may better predict castration resistance.

Emergency Placed Percutaneous Nephrostomy Catheter Provides Safe and Effective Access for Future Percutaneous Nephrolithotomy Operation

Objective: It was aimed to investigate the feasibility of the percutaneous nephrostomy (PCN) catheter placed in an emergency in the future percutaneous nephrolithotomy (PNL) operation. Material and Methods: Patients who underwent PCN catheter insertion by an interventional radiologist under emergency situations prior to PNL surgery between January 2013 and December 2018 were included in the study. Demographic characteristics, indication for PCN insertion, stone characteristics, pre- and post-operative laboratory values, intra-operative data, usability/non-usability of PCN catheter for renal access, post-operative data and complications were recorded. Results: A total of 32 patients were included in the study. (PCN usable: 21, unusable: 11). Indications for catheter insertion were obstruction in 26 (81.25%) patients and urinary tract infection in 6 (18.75%) patients. Renal access was achieved in 21 (65.62%) patients by using the PCN catheter tract during PNL. The most common PCN access was used in the inferior pole. In 11 (34.37 %) patients, the PCN tract was not usable for access. In patients in whom PCN was unusable due to an unsuitable calyx for access, the most common new access site was the inferior calyx in 6 patients, the superior calyx in 3 patients and the middle calyx in 2 patients. There was no statistically significant difference between the two groups in which the PCN catheter was usable and unusable for PNL access (p&amp;gt;0.05), except for the mean length of hospital stay (p=0.039). Conclusions: PCN catheters inserted prior to PNL surgery can be used effectively and safely for renal access during surgery. However, in emergency cases, it is important that the PCN catheter is inserted through the appropriate calyx in patients undergoing future surgery.

Kidney transplantation in patients on anti-tubercular therapy: A single centre observational study.

Tuberculosis (TB) is a common infection in chronic kidney disease. The prolonged therapy of TB can delay kidney transplantation in patients on antitubercular therapy (ATT). This was a retrospective single-center study to analyze the safety of kidney transplantation and its outcomes in patients undergoing transplantation while on the continuation phase of ATT. Between 2013 and 2022, 30 patients underwent kidney transplantation while on ATT. Median age was 38 years and 70% were males. Majority of the patients (86.7%) had extrapulmonary tuberculosis, most common site of involvement being tubercular lymphadenitis. 14/30 patients had microbiological/histopathological diagnosis of TB and the rest were diagnosedby ancillary tests. Patients were treated with 4 drug ATT (isoniazid, rifampicin, pyrazinamide, ethambutol) before transplantation for aminimum of 2 months. Post-transplantation fluoroquinolone-based non-rifamycin ATT was used (median duration 11 months). All patients completed therapy. At 2 years, there was 100% patient survival and 96.7% graft survival. Median eGFR at 6, 12, and 24 months post-transplantation was 71.9, 64.7, and 67mL/min/1.73m2, respectively. The percentage of patients suffering a biopsy proven acute rejection at 6, 12, and 24 months was 3.3%, 6.7%, and 6.7%. Kidney transplantation can be done in patients with TB who have a satisfactory response to the intensive phase of the ATT. The decision for transplantation while on the continuation phase ofATT should be individualized. In our experience, there is excellent patient and graft survival in these patients with a low risk of failure of ATT or relapse of TB.

Accuracy Evaluation of an Estimation System for Dental Treatment Sites by Using Image Recognition.

In dentistry, misidentification of the treatment site may occur an adverse event with irreversible consequences. Among these, the left-right tooth error is the second most common site misidentification. In this study, we developed a treatment site estimation system using image recognition, and the accuracy rate of the left and right teeth was more than 85%. The results suggest that this system can be used to prevent the misidentification of the left and right teeth.

The immunohistochemical expression Ki-67 In Polymorphous Low Grade Adenocarcinoma of the Salivary Glands

Background: Polymorphous Low Grade Adenocarcinoma is a rare malignant tumor of minor salivary glands. It has an unique histopathological, clinical and behavioural features. Most of its incidence has been presented in the palate. It shows a variety of growth patterns within the same one lesion, including cribriform, tubular, and solid areas that may mimic adenoid cystic carcinoma. The tumor cells histologically are characterized by lacking of nuclear atypical and hyperchromatism with rare mitoses. However, the prognosis of this tumor is good because of its low grade, although it has an unpredictable potential to metastasize.&#x0D; Objectives: To evaluate the histopathological expression of Ki-67 proliferation antigen in Polymorphous low grade adenocarcinoma and compare the results with the clinicopathological parameters and grading of the tumors.&#x0D; Materials and Methods: This study includes 20 cases with Polymorphous Low Grade Adenocarcinoma of minor salivary glands diagnosed histopathologically and treated surgically, were investigated for the immunohistochemical expression of Ki-67 antigen. Immunohistochemical staining was performed using a Labeled Strept- Avidin Biotin method (LSAB) and 0.05 (two-sided) was the level of significance.&#x0D; Results: Twenty cases of Polymorphous Low Grade Adenocarcinoma of salivary glands were histologically diagnosed in this retrospective study to evaluate the expression of Ki-67. The mean age for patients with PLGA was nearly (50.6). (12) (60%) cases were males and (8) (40%) cases were females and also male to female ratio was (1.5:1).&#x0D; In regarding to site distribution, the most common site was the palate followed by the submandibular gland and floor of the mouth. &#x0D; Conclusions: it was observed that there is a higher rate of cellular proliferation in malignant tumors with high grade, indicating their role in the malignancy and aggressive behavior of these tumors.

Challenges in the maintenance of an open hospital-based cancer registry system in a low-to-middle-income country (LMIC): 2017-2022 experience.

Hospital-based cancer registries (HBCRs) record data on all patients diagnosed and/or treated for cancer at healthcare facilities and evaluate the burden of the disease and the quality of healthcare services at that hospital, helping improve patient care, and providing an assessment of healthcare quality. The CARE PH app was created as a tool to facilitate a system of hospital-based cancer registries in the Philippines, a lower middle-income country. From 2017 to 2022, a total of 60,021 cancer registrants from 44 CARE PH hospitals were entered into the database. Breast cancer was the most common primary site, accounting for 17,660 cases (29.4%). This was followed by colorectal cancer at 11.1%, cervical cancer at 6.2%, head and neck cancer at 5.9%, and prostate and other male genital cancer at 5.1%.Among the 30 data fields collected, 17 exhibited 0-20% missing data, eight displayed 21%-90% missing data, while five depicted 91%-100% missing data. Most of the data fields with missing data are in the treatment and follow-up modules, which are stored in separate forms in a patient's record. Digital transformation of hospitals from paper-based charts to electronic medical records, and the integration of the HBCR to the EMR and hospital information system, will likely be the best solution for these limitations. It is recommended that the creation and maintenance of HBCRs nationwide must be harmonized, and embedded in all relevant national programs and legislations. The development of an information technology process that is based on a cancer patient's journey, should be built on an open system embedded in a well designed enterprise architecture, functioning under the guidance of a strong leadership and governance team. All these must be present in order to create and maintain a robust HBCR that is useful for furthering cancer registry and research in the country.

Temporal Trends in Mortality of Critically Ill Patients with Sepsis in the United Kingdom, 1988-2019.

Rationale: Sepsis is a frequent cause of ICU admission and mortality. Objectives: To evaluate temporal trends in the presentation and outcomes of patients admitted to the ICU with sepsis and to assess the contribution of changing case mix to outcomes. Methods: We conducted a retrospective cohort study of patients admitted to 261 ICUs in the United Kingdom during 1988-1990 and 1996-2019 with nonsurgical sepsis. Measurements and Main Results: A total of 426,812 patients met study inclusion criteria. The patients had a median (interquartile range) age of 66 (53-75) years, and 55.6% were male. The most common sites of infection were respiratory (60.9%), genitourinary (11.5%), and gastrointestinal (10.3%). Compared with patients in 1988-1990, patients in 2017-2019 were older (median age, 66 vs. 63 yr), were less acutely ill (median Acute Physiology and Chronic Health Evaluation II acute physiology score, 14 vs. 20), and more often had genitourinary sepsis (13.4% vs. 2.0%). Hospital mortality decreased from 54.6% (95% confidence interval [CI], 51.0-58.1%) in 1988-1990 to 32.4% (95% CI, 32.1-32.7%) in 2017-2019, with an adjusted odds ratio of 0.64 (95% CI, 0.54-0.75). The adjusted absolute hospital mortality reduction from 1988-1990 to 2017-2019 was 8.8% (95% CI, 5.6-12.1). Thus, of the observed 22.2-percentage point reduction in hospital mortality, 13.4 percentage points (60% of total reduction) were explained by case mix changes, whereas 8.8 percentage points (40% of total reduction) were not explained by measured factors and may be a result of improvements in ICU management. Conclusions: Over a 30-year period, mortality for ICU admissions with sepsis decreased substantially. Although changes in case mix accounted for the majority of observed mortality reduction, there was an 8.8-percentage point reduction in mortality not explained by case mix.

Clinical presentation and outcome of invasive mould disease in paediatric patients with acute lymphoblastic leukaemia

BackgroundChildhood acute lymphoblastic leukaemia (ALL) cure rates have improved, but invasive mould disease (IMD) remains a life-threatening complication. Here, we evaluate the epidemiology, clinical presentation, treatment and outcome of IMD in paediatric patients with ALL. MethodsPatients (1–18 years) treated according to the Dutch Childhood Oncology Group (DCOG) ALL-11 protocol from 2012–2021 were analysed for probable and proven IMD. Data was extracted from the Dutch national registry and the electronic health care system. ResultsAmong 643 patients with ALL, 47 (7.3%) were diagnosed with a probable (n = 29) or proven (n = 18) IMD. Aspergillosis was diagnosed in 42 (89%) patients. Forty-one episodes (87%) occurred during the induction (n = 20) and first consolidation (n = 21) course. The median age at ALL diagnosis was 5 years [IQR 3–10] in the overall group versus 14 years [IQR 7–16] in the IMD group. Two-third of the patients did not receive mould-active prophylaxis. The most prevalent clinical symptoms at presentation were persistent fever and respiratory symptoms. The lungs were the most common site of infection with involvement in 44 (94%) patients, followed by the CNS in 16 (34%) patients. The 6-week and 12-week mortality rate after IMD diagnosis was 10.6% and 14.9%, respectively. Discussion and conclusionIn our paediatric cohort a notable incidence of probable and proven IMD was observed during the early stages of treatment. Remarkable is the high frequency of CNS involvement. These findings highlight the importance of effective prophylactic strategies and warrant early brain imaging.

SENTINEL LYMPH NODE BIOPSY IN THE MANAGEMENT OF PATIENTS WITH MALIGNANT MELANOMA

Objectives: To evaluate the efficacy of sentinel lymph node biopsy in the treatment of malignant melanoma. Materials and Methods: Thirty-two melanoma patients without distant or clinical lymph node metastasis underwent preoperative lymphoscintigraphy using Tc99m and a handheld gamma probe to identify sentinel lymph nodes for biopsy. In cases with detected sentinel lymph node metastasis, the patient may require total complete lymph node dissection, combined with optional systemic therapy. Follow-up was performed to evaluate the efficacy of this procedure. Results: In 32 melanoma patients, the most common site of primary tumors was the extremity, accounting for 90.6%, with a mean Breslow index (thickness of the primary tumor) of 1.84 mm. The incidence of microscopic lymph node metastasis was 34.4%. For cases with no detected sentinel lymph node metastasis, 100% of patients had a stable condition, and no recurrence or metastasis was detected. In 11 cases with occult nodal metastasis: 2 deaths, 4 patients were treated with chemotherapy, and 5 cases without chemotherapy. The mean duration of hospitalization for the group with sentinel lymph node metastasis was greater than that of the group without sentinel lymph node metastasis, 25.1 ± 3.1 days and 13.5 ± 1.3 days, respectively. Conclusion: Our results suggest that sentinel lymph node biopsy is a less invasive technique for melanoma patients with no clinically detectable lymph node and distant metastases. This procedure has shown initial outcomes, but it is necessary to conduct a study with a larger sample size and a longer follow-up time, as well as comparing it with a control group for accurate evaluation. Received 23 June 2023Revised 22 September 2023Accepted 27 November 2023

Intrahepatic cholangiocarcinoma: Recurrence patterns, genomics and survival.

570 Background: Recurrence is common after resection of intrahepatic cholangiocarcinoma (IHC) but how recurrence patterns impact survival remains unclear. This study investigated the clinicopathologic and genomic factors associated with site of first recurrence and their impact on outcome after curative intent resection. Methods: Patients who underwent curative intent hepatectomy for IHC at two medical centers (MSKCC and EMC) with complete follow up and tumor genomic data were included. Documented sites of first disease recurrence were classified as liver only (LO), extrahepatic (EH) only or simultaneous liver and extrahepatic (SIM). Time to recurrence (TTR) and recurrence-free (RFS) were calculated from time of resection while OS was calculated from time of recurrence. Primary tumors underwent targeted next generation sequencing. Clinical, histopathologic and genomic factors associated with site(s) of recurrence, RFS and OS were assessed. Results: A total of 318 patients (n=296 MSK, n=22 EMC) treated between 1993 and 2021 met inclusion criteria and were analyzed; 232 patients (73%) developed recurrence. TTR was 11 (9.8, 12) months; OS and RFS was 26 (20, 33) and 14 (13, 18) months, respectively, among patients that recurred. Sites of first recurrence were LO 93 (40%), EH 80 (34%) and SIM 59 (26%). Median OS was similar in the LO (33 [26,42] months) and EH groups (33 [23,46] months) but much lower in SIM (12 [9.8,18] months) (p &lt; 0.001). Moderate/poor tumor differentiation (p = 0.004), LVI (p = 0.004), N1 disease (p = 0.003), and PNI (p = 0.012) were associated with SIM; only positive resection margin predicted LO (p = 0.007). No individual genomic or pathway alterations predicted site of initial recurrence; however, for all patients, TP53 mut (HR 2.01, 1.4-2.9; p &lt; 0.001), CDKN2A del (HR 1.96, 1.29-2.98; p = 0.003), CDKN2B del (HR 3.2, 2.03-5.05; p &lt; 0.001) and KRAS mut (HR 2.49, 1.56-3.96; p &lt; 0.001) were associated with worse survival. On multivariable analysis, SIM (HR 2.23, 1.49-3.34; p &lt; 0.001), clinical stage III (HR 1.94, 1.26-2.99; p = 0.011), and alterations in TP53 (HR 2.07, 1.4-3.07; p &lt; 0.001), CDKN2B (HR 4.1, 2.53-6.63; p &lt; 0.001) and KRAS (HR 2.72, 1.68-4.43; p &lt; 0.001) were independent predictors of worse OS. Of note, 13 LO patients were treated with regional chemotherapy after recurrence, with an associated median OS of 49 (33, NR) months compared to 28 (20, 39) months in the 80 patients treated with systemic therapy alone. Conclusions: Recurrence after resection of IHC was common, and the liver was the single most common site (66%). Clinicopathologic and genomic variables had limited ability to predict site of first recurrence. While LO and EH were associated with similar OS, simultaneous recurrences were dramatically worse. The data support adjuvant strategies targeting liver recurrence to improve outcome after resection of IHC.

Association of plasma uracil concentration with 5-FU pharmacokinetics, dose-limiting toxicity, and DPYD genotype in patients with gastrointestinal cancer.

751 Background: Plasma uracil concentration &gt;16 ng/mL is used in some countries as a screening test for DPD deficiency. We conducted this exploratory study to evaluate the association of uracil concentration with 5-FU exposure, toxicity, and DPYD genotype in patients without known DPD deficiency. The main hypothesis was that lower uracil concentration would be predictive of subtherapeutic 5-FU drug exposure (5-FU AUC &lt; 20 mg*h/L) in patients treated with infusional 5-FU. Methods: The study prospectively enrolled patients with GI cancer who were receiving initial chemotherapy with a regimen containing a 46-hour 5-FU infusion initially dosed at 2400 mg/m2. Study candidates were screened for the DPYD *2A, *13 and c.2846A&gt;T gene variants; variant carriers were excluded. Participants gave pretreatment fasting morning blood samples for determination of plasma uracil concentration and DPYD whole-gene sequencing. Plasma samples were collected at hour 45 of 5-FU infusion in chemotherapy cycles 1 and 2 for determination of 5-FU exposure, measured as the 5-FU AUC. We estimated a linear mixed-effects model to test the association of uracil concentration with 5-FU AUC, adjusting for cycle, sex, creatinine, and 5-FU infusion dose (in mg/m2). Results: There were 29 evaluable participants with a median age of 64 years (range 41-81); nine (31%) were female. The most common cancer sites were colorectal (n = 15) and pancreatic (10). The median (IQR) plasma uracil concentration was 10.4 ng/mL (7.2, 12.6). Data for 5-FU AUC were available for 19 subjects in cycle 1 (median = 22.0 mg*h/L) and 27 subjects in cycle 2 (median = 19.3 mg*h/L). In the mixed-effects model, male sex was significantly associated with 5-FU AUC (beta = -12.0 [95% CI -17.2, -6.7], p &lt;0.001) but plasma uracil concentration was not (beta = 0.35 [-0.16, 0.86], p=0.16). Holding other covariates constant, male sex was associated with a 29% decrease in 5-FU AUC (vs female) and plasma uracil concentration in the lowest quartile was associated with a 12% decrease in 5-FU AUC (vs highest quartile). Three of 29 participants (10%, all male) had uracil concentrations of &gt;16 ng/mL, suggestive of DPD deficiency. The subject with the highest uracil concentration (23.1 ng/mL) had severe toxicity in cycle 1 (neutropenia, mucositis) requiring 5-FU dose reduction; whole gene sequencing identified a rare DPYD missense variant in this subject (c.2185G&gt;A [p.A729T]). The other two subjects with uracil concentration &gt;16 ng/mL did not have culprit DPYD gene variants and tolerated infusional 5-FU at 2400 mg/m2 without early dose-limiting toxicity. Conclusions: Our findings suggest that male sex is more important than low pretreatment plasma uracil concentration as a predictor of risk for subtherapeutic 5-FU drug exposure. This result is consistent with prior evidence that men experience less 5-FU associated toxicity than women.

Preliminary results of a phase II study of surufatinib plus sintilimab, nab-paclitaxel and gemcitabine (AG) as first-line therapy in patients (pts) with locally advanced or metastatic pancreatic adenocarcinoma (mPDAC).

659 Background: Advanced pancreatic adenocarcinoma (PDAC) had poor survival and limited therapeutic options. Surufatinib is a potent, small-molecule tyrosine kinase inhibitor (TKI), selectively targeting VEGF receptors (VEGFR) 1, 2, and 3, FGFR 1, and CSF-1R. Recent studies showed that small molecule anti-vascular inhibitor combined with a PD-1 inhibitor exhibited encouraging efficacy in PDAC. This study is to assess the efficacy and safety of surufatinib plus sintilimab (an anti-PD-1 antibody),nab-paclitaxel and gemcitabine(AG) as first-line therapy for mPDAC pts. Here we report the preliminary results. Methods: Eligible pts ≥18 years old with histologically confirmed mPDAC, ECOG PS 0-1, with at least one measurable lesion were enrolled. Pts received surufatinib (250mg, orally daily), sintilimab (200mg, I.V., D1, Q3W), nab-paclitaxel (125mg/m2, I.V., D1, D8, Q3W) and gemcitabine (1000mg/m2,I.V.,D1, D8, Q3W). Based on Simon’s Two-stage design, 11 patients would be enrolled in stage 1; if 3 or more responses were observed, the trial would continue to stage 2, and additional 21 patients would be enrolled. The total sample size was 32. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: At cutoff date of Aug 25, 2023, 15 pts were enrolled and received at least one time treatment. Median age was 60 years (range 45-68), male 53.3%, ECOG PS 1 100%, 66.7% of pts had more than 3 sites of metastasis. The most common metastatic sites were lymph nodes (66.7%) and liver (60.0%). 12 pts had received at least one tumor assessment. Six out of 11 evaluable pts responded during stage 1, allowing for enrollment to continue with a planned 21 additional patients in stage 2. Eight pts achieved partial response (PR), 3 pts achieved stable disease (SD), and the confirmed ORR (c-ORR) was 50.0% (6/12) (95% confidence interval [CI]: 21.1-78.9), and the DCR was 91.7% (11/12) (95% CI: 61.5-99.8). The median time to response (TTR) was 2.95 months (95% CI: 2.79-3.06), and median PFS was not reached yet. 15 pts underwent safety evaluation. The most common AEs of all grades were white blood cell count decreased (66.7%), neutrophil count decreased (60.0%), and anemia (53.3%), and grades ≥ 3 were blood cell count decreased (33.3%), neutrophil count decreased (33.3%), and diarrhea (13.3%). Conclusions: Surufatinib plus sintilimab, along with AG showed preliminary anti-tumor activity and manageable toxicity for the 1L treatment of mPDAC. This trial is ongoing and warrants further exploration in mPDAC. Clinical trial information: NCT05481476 .

Surufatinib plus sintilimab in patients with advanced gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): A single-arm, open-label, single-center phase II trial.

358 Background: Anti-PD-1 antibodies plus chemotherapy have become the standard first-line treatment for advanced GC/GEJC with CPS score ≥ 5. However, GC/GEJC still has dismal survival. Preclinical studies have demonstrated that surufatinib (a novel small-molecule kinase inhibitor targeting VEGFR1-3, FGFR and CSF-1R) combined with anti-PD-1 antibodies have synergistic antitumor effects by modulating tumor immune microenvironment. Therefore, a phase II trial to evaluate surufatinib plus sintilimab in patients (pts) with advanced GC/GEJC was conducted. Here we report the results of part A of this trial. Methods: This single arm, open-label, single center phase II trial consisted of two parts: part A (second-line therapy) and part B (first-line therapy). In part A, pts aged 18-75 years who were HER2-negative, failed first-line standard therapy, and immune checkpoint inhibitor therapy naive were enrolled. Part A included safety run-in and dose expansion stages. Six pts in the safety run-in received surufatinib at 250mg once daily as starting dose, in combination with a fixed dose of sintilimab (200 mg, d1, Q3W). If more than 1 DLT occurred in stage 1, the recommended dose of surufatinib for stage 2 (N=11) would de-escalate to 200 mg, otherwise would maintain as 250mg. The primary endpoint was ORR per RECIST v1.1. Secondary endpoints included DCR, PFS, OS and safety. If the ORR of part A was ≥ 30%, the trial would proceed to Part B (N=44), further evaluating this combination treatment in previously untreated advanced GC/GEJC. Results: At data cutoff on 8/10/2023, 16 pts (6 in safety run-in; 10 in dose expansion) were enrolled in part A. The median age was 56 years; 75% male; 69% with ECOG PS 1. Peritoneum (56%) was the most common metastatic site. No DLTs were observed in the safety run-in stage, so the recommended dose of surufatinib for dose expanding stage was 250 mg. Among the 16 pts evaluable for tumor response, 6 pts achieved PR, 4 pts achieved SD. The confirmed ORR and DCR per RECIST v1.1 was 40.0% (95% CI: 15.2- 64.6%) and 66.7% (95% CI: 38.4- 88.2%), respectively. Median DOR was not reached and 50% of responders were estimated to have a response duration ≥ 7.8 months. Median PFS and OS were not yet mature. Most TEAEs (≥ 40%) were grade 1-2, including hypoproteinemia (62.5%), hypertension (50%), proteinuria (50%), lymphocyte count decreased (43.8%). The most common grade ≥ 3 TEAEs reported by 5 pts (31.3%) were blood bilirubin increased (18.8%), hypertension, lymphocyte count decreased, and alanine transaminase elevation (6.3%, respectively). No treatment-related death was reported. Conclusions: The results showed surufatinib plus sintilimab acquired preliminary efficacy and manageable safety profile as the second-line treatment for advanced GC/GEJC. Part B is ongoing, and more data analysis will be reported further. Clinical trial information: NCT05235906 .

Real-world treatment patterns and unmet need in patients with previously treated metastatic colorectal cancer that is not MSI-H or dMMR.

53 Background: Regorafenib and trifluridine/tipiracil (TAS-102) are standard of care (SoC) systemic anticancer treatments (SACT) for metastatic colorectal cancer (mCRC) patients perviously treated with fluoropyrimidine (5-FU), irinotecan, &amp; oxaliplatin-based chemotherapy. However, evidence is limited on post-chemotherapy &amp; later SACT for patients with mCRC that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This study assessed real-world patient characteristics and treatment patterns in community oncology practices among previously treated, not MSI-H/dMMR mCRC patients. Methods: This retrospective cohort study utilized The US Oncology Network (iKnowMed) electronic health record database, supplemented by chart review. The study cohort comprised adult, not MSI-H/dMMR mCRC patients treated with chemotherapy (5-FU/capecitabine, irinotecan, and oxaliplatin) who initiated subsequent SACT or received best supportive care (BSC) between 1/1/2016 &amp; 12/31/2021. Index date for SACT users was the regimen start date. For patients on BSC and no subsequent SACT/BSC, index date was last chemotherapy administration date. Patients were followed from index date through 8/31/2022, date of death or last contact date, whichever occurred first. Descriptive statistics were used to report patient and treatment characteristics. Results: The study consisted of 292 mCRC patients, with a median age of 57 (range: 49, 68) years. The predominant histology was adenocarcinoma (n = 237, 81.2%) with 1.7% other histology and rest missing, 198 (67.8%) patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and 206 (70.5%) had primary tumors located in the colon. Liver (n = 207, 70.9%) and lung (n = 78, 26.7%) were the most common metastasis sites. Diabetes (n = 33, 11.3%) and peripheral vascular disease (n = 18, 6.2%) were the most common comorbidities. Eighty-seven (29.8%) patients received at least one chemotherapy in the adjuvant/neo-adjuvant setting, while majority (70.2%) patients received chemotherapies in the metastatic setting. Overall, 203 (69.5%) received SACT post-chemotherapy, 84 (28.8%) received BSC and 5 (1.7%) did not receive SACT/BSC. Among the SACT post-chemotherapy users, 30 (14.8%) received regorafenib, 25 (12.3%) received TAS-102 and 148 (72.9%) received other SACT. Other SACT included irinotecan-based (n = 76, 37.4%), oxaliplatin-based (n = 30, 14.8%), irinotecan and oxaliplatin-based (n = 6, 3.0%) chemotherapy, and anti-EGFR (n = 15, 7.4%) or anti-VEGF (n = 8, 3.0%) targeted therapies. Conclusions: Overall, only 27.1% of previously treated mCRC patients with tumors that were not MSI-H or dMMR received SoC. The real-world variability in choice of treatments and the high percentage of patients rechallenged with chemotherapy in subsequent lines, highlights an unmet need in this population.

Epidemiology of spinal cord injury and spinal cord injury–induced urinary tract stones in Taiwan: A 2005–2015 population-based cohort study

Context Patients with spinal cord injury (SCI) can develop urinary tract stones (UTSs) up to years after the injury, which is especially common in the first few months. However, relevant epidemiological studies and up-to-date epidemiological data for SCI in Taiwan are lacking. Purpose To estimate SCI and SCI-induced UTS incidence and trauma severity, neurological deficits, and injury site in patients with SCI-induced UTSs in Taiwan. Design Retrospective cohort study. Patient sample: Taiwan National Health Insurance Research Database (NHIRD) data and death data from the Department of Health and Welfare Data Science Center (HWDC) collected over 2005–2015 from 13,977 patients with SCI aged >18 years. Outcome measures Cumulative incidence (CI), incidence density (ID), relative ratios (RRs), odds ratios (ORs), and hazard ratios (HRs) were measured. Methods By using Cox regression, we assessed UTS risk in patients with SCI. Results Although standardized SCI incidence demonstrated a decreasing trend annually, the average annual incidence remained at 60.4 per million. Most (65.7%) of the included patients were men. SCI incidence was 1.98 times higher in men than in women. The most common injury site was the cervical spine (63.8%); the incidence at this site was 2.83 times higher in men than in women. Most (76.1%) of the patients had traumatic SCI (TSCI), and the standardized incidence of TSCI and non-TSCI was 45.9 and 14.4 per million, respectively. 46.1% of the patients had severe SCI (RISS ≥ 16). Over the 11-year follow-up period, UTSs occurred in 10.4% of the patients, with a standardized incidence of 2.39 per 100 person-years, and UTS risk was 1.56 times higher in men than in women. Age of 45–65 years, SCIs at multiple sites, and neurological deficits (e.g. paraplegia) were noted to be UTS risk factors. Finally, UTS onset mainly occurred in the first year after SCI. Conclusion The risk of UTS among patients with SCI is influenced by age, sex, injury site, and paraplegia but not by paralysis resulting from other neurological deficits. Even though SCI incidence is declining annually, severe SCI remains a significant issue. Therefore, continuing to reduce SCI incidence and strengthening urinary tract management in patients with SCI are essential for reducing UTS occurrence and their impact on health.

A phase 2, open-label, safety and efficacy study of telotristat ethyl plus first-line chemotherapy in patients with advanced biliary tract cancer.

472 Background: Patients (pts) with unresectable biliary tract cancer (BTC) have a poor prognosis. In preclinical models of cholangiocarcinoma (CCA) telotristat ethyl (TE), a tryptophan hydroxylase inhibitor that reduces production of serotonin, enhanced the antiproliferative effects of gemcitabine and cisplatin (GC) chemotherapy. This trial assessed the safety and efficacy of adding TE to GC chemotherapy in pts with advanced BTC. Methods: This was a Phase 2 open-label study. Eligible pts had unresectable, locally advanced, or metastatic BTC, were treatment naïve and had plans to initiate GC chemotherapy. On Day 1, pts received Gem 1000mg/m2 and Cis 25mg/m2 with TE 250 mg orally three times daily (TID) for 7 days. Thereafter, pts received TE 500 mg TID continuously plus GC therapy on days 1 and 8 of each 21-day cycle. The study comprised of 2 stages: stage 1 would enroll 20 patients with a safety run-in cohort in the first 6 pts to monitor safety and tolerability of TE + GC treatment for 21 days. Stage 2 would enroll 33 patients if no significant/unresolved grade 3 or higher toxicities related to study drug occurred in stage 1. The primary endpoint was 6-month (mo) progression free survival (PFS) rate according to RECIST 1.1. If 60% of pts (≥34) in the safety population were alive and progression free at 6-mos, the study was considered successful. Secondary endpoints included overall response rate (ORR) and disease control rate (DCR). Restaging occurred every 9 weeks using RECIST 1.1 and toxicities were graded using CTCAE v 5.0. Results: Between 2019 and 2021, fifty-three pts were enrolled across 12 study sites and comprised the safety population. The majority of pts were female (62.3%) and median age was 66 yrs (range 33 to 79). Baseline mean plasma 5-HIAA was 11.1 µg/L (ULN defined as &gt;10.8 µg/L). Thirty-one pts (58.5%) had plasma 5-HIAA levels ≤ULN and 22/53 (41.5%) had 5-HIAA levels &gt;ULN. Majority of pts had metastatic BTC (85%) and liver was the most common primary tumor site (66%). The 6-month PFS rate was 22.6% (12/53). Based on blinded independent central review, the ORR was 13.2% and DCR was 62.3%. Mean reduction in plasma 5-HIAA at 6 mos was -1.735 µg/L (SD 8.69) in 24 patients with available data. There was no difference in 6-mo PFS rate based on pts baseline 5-HIAA status; 58% (14/24) pts had ≥30% decrease from baseline in 5-HIAA, however there was no correlation with 6-month PFS. The most common TE related TEAEs were constipation (43.4%), nausea (28.3%) and fatigue (28.3%). Conclusions: The study did not achieve its primary endpoint of 60% of patients on TE plus GC chemotherapy being alive and progression free at 6 months. TE did reduce 5-HIAA levels in a subset of pts; however, this did not correlate to improved clinical outcomes. No significant safety issues noted with TE in combination with GC chemotherapy. Clinical trial information: NCT03790111 .