Resection Of Metastatic Lesions Research Articles

Occult gastric carcinoma with microsatellite instability diagnosed 10 years after excision of metastatic lymph node: a case report

BackgroundSuprapancreatic lymph node metastasis is one of the usual routes for gastric cancer. However, it is rare for the primary lesion to be found several years after resection of the suprapancreatic metastatic lymph node. This is a report of occult gastric carcinoma with microsatellite instability diagnosed 10 years after excision of a metastatic lymph node.Case presentationA 55-year-old female presented with suprapancreatic lymph node swelling during a medical examination. Gastroscopy revealed no malignancy. We performed an excisional biopsy via laparotomy and histologically suspected metastatic cancer of unknown origin. After nine and a half years, we detected early gastric cancer by gastroscopy and performed a distal gastrectomy. The gastric tumor was pathologically similar to the previous suprapancreatic tumor. Immunohistochemical examination revealed that both the stomach and suprapancreatic lymph node exhibited microsatellite instability, suggesting that the two lesions were of the same origin.ConclusionsThis case is considered valuable because there have been no previous reports of gastric cancer with characteristics of high microsatellite instability in which the primary tumor was identified a long time after resection of metastatic lesions.

45 INTerpath-004: A phase 2, randomized, double-blind study of pembrolizumab with V940 (mRNA-4157) or placebo in the adjuvant treatment of renal cell carcinoma

Abstract Background The PD-1 inhibitor pembrolizumab is approved as monotherapy for the adjuvant treatment of patients with renal cell carcinoma (RCC) who are at increased risk of recurrence following nephrectomy or nephrectomy and resection of metastatic lesions based on results from the phase 3 KEYNOTE-564 trial. Novel combination strategies could provide further clinical benefit in the adjuvant setting. V940 (mRNA-4157) is an individualized neoantigen therapy that is hypothesized to increase the antitumor activity of T cells and enhance the activity of pembrolizumab. V940 plus pembrolizumab showed improved clinical outcomes for stage III/IV melanoma compared with pembrolizumab alone in the phase 2b KEYNOTE-942 study. INTerpath-004 is a global, multicenter, randomized, double-blind, phase 2 trial (NCT06307431) designed to evaluate the efficacy and safety of adjuvant pembrolizumab with V940 or placebo in patients with RCC who have undergone nephrectomy. Methods Eligible patients are adults with histologically or cytologically confirmed RCC with clear cell or papillary histology (intermediate-high risk [pT2 Gr4, N0, M0 or pT3 Gr3/4, N0, M0], high-risk [pT4, N0, M0 or pT any stage, N1, M0], or M1 NED [solid, isolated, soft tissue metastases that can be completely resected at the time of nephrectomy or ≤2 years from nephrectomy]) with or without sarcomatoid features. Patients must have undergone nephrectomy and/or metastasectomy ≤12 weeks prior to randomization and be tumor-free as assessed by investigator. Patients must not have received prior systemic therapy ≤4 weeks or radiotherapy ≤2 weeks prior to randomization. Approximately 272 patients will be randomly assigned 1:1 to receive pembrolizumab 400 mg intravenously every 6 weeks for up to 9 cycles in combination with either V940 1 mg or placebo intramuscularly every 3 weeks for up to 9 doses or treatment discontinuation due to unacceptable toxicity, disease recurrence, patient withdrawal, or investigator decision. Randomization will be stratified by histology (clear cell vs papillary) and disease risk (intermediate-high vs high vs M1 NED). Imaging assessments (computed tomography or magnetic resonance imagery) will be performed every 12 weeks through year 2, every 16 weeks in years 3-5, and every 24 weeks in year 6 and beyond. The primary endpoint is disease-free survival by investigator assessment. Secondary endpoints include distant metastasis-free survival, overall survival, and safety parameters including adverse events (AEs), laboratory test results, and vital signs. AEs will be monitored throughout the study and for 30 days after the last dose of treatment (90 for serious AEs) and graded per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Efficacy will be assessed in all randomly assigned patients, and safety will be assessed in all patients who received ≥1 dose of study intervention. Recruitment is ongoing.

FOLFOXIRI/bevacizumab (bev) versus doublets/bev as initial therapy of unresectable liver-only, right-sided and/or RAS or BRAF mutated (mut) metastatic colorectal cancer (mCRC): An individual patient data-based pooled analysis of randomized trials.

e15563 Background: FOLFOXIRI/bev was associated with longer PFS and OS versus doublets/bev independently of the presence of liver-limited disease or not, and the secondary resection of metastatic lesions. Recently, in the CAIRO-5 study patients with liver-limited right-sided and/or RAS or BRAF mutated mCRC experienced no OS difference, but higher ORR, R0 resection rate, and longer PFS with the triplet/bev when compared with doublets/bev. Here we aim at providing an estimation of the efficacy and activity of FOLFOXIRI/bev over doublets/bev in patients with unresectable liver-only, right-sided and/or RAS or BRAF mut mCRC. Methods: We selected pts with liver-only, right-sided and/or RAS or BRAF mut mCRC, and treated with first-line doublets/bev or FOLFOXIRI/bev in four phase II or III randomized controlled trials (RCTs): TRIBE (NCT00719797), TRIBE2 (NCT02339116), CHARTA (NCT01321957), and STEAM (NCT01765582). Patients included in these RCTs were deemed initially unresectable according to a multidisciplinary evaluation and were not selected based on the potential conversion to resectability. We compared FOLFOXIRI/bev with doublets/bev in terms of PFS, OS, ORR, and R0 resection. Results: A total of 300 pts were eligible. The median age was 61 years and most of them had an ECOG performance status of 0 (83%) and synchronous metastases (91%). One hundred and thirty (43%) and 170 (57%) pts received doublets/bev and FOLFOXIRI/bev, respectively. Baseline characteristics were homogeneous between the two treatment groups. Pts receiving FOLFOXIRI/bev showed longer PFS (12.3 vs 10.3 months [mos] HR:0.75, p = 0.019) and a statistically not significant trend for better OS (29.1 vs 23.2 mos, HR:0.85, p = 0.253), than those treated with doublets/bev. FOLFOXIRI/bev was also associated with higher ORR (64% vs 53%, OR:1.54, p = 0.076) and no differences in R0 resection rate (27% vs 24%, OR:1.15, p = 0.696) was reported. No significant interaction was found between treatment effect and the achievement of R0 resection in terms of both PFS (Pinteraction:0.81) and OS (Pinteraction:0.53). Conclusions: As compared to doublets/bev, upfront FOLFOXIRI/bev provides a meaningful advantage to pts with initially unresectable, liver-only, right-sided and/or RAS or BRAF mut mCRC, in terms of activity and efficacy, thus corroborating the choice of this regimen as upfront treatment for these pts, regardless of the opportunity to achieve the R0 secondary resection of their liver metastatic lesions.

The Safety and Effectiveness of Bevacizumab in Metastatic Colorectal Cancer With Unresectable Metastases: A Real-Life Study From the South of Morocco.

Background Colorectal cancer constitutes a significant public health challenge, despite remarkable strides made in the last two decades, particularly in the medical management of metastatic stages. Notable progress has been achieved through targeted therapies such as anti-epidermal growth factor receptors or anti-angiogenic antibodies, as well as advancements in surgical approaches for hepatic metastases. This study seeks to assess the efficacy and safety of bevacizumab plus chemotherapy in individuals with metastatic colorectal cancer. Methodology This is an observational, cross-sectional, retrospective study of all patients who were followed up for metastatic colorectal cancer with unresectable metastases and were treated with bevacizumab in combination with standard chemotherapy from January 2010 until December 2019 in the medical oncology department of the Centre Hospitalier Universitaire (CHU) Souss-Massa of Agadir. Results Of the total 162 cases, 117 (72%) had metastatic disease, and 45 (28%) progressed to metastatic disease after initial treatment. The median age of the patients was 55 years (range = 23-79 years) with a sex ratio of 1.1 (M/F). The tumor was located in the left colon in 135 (83.3%)patients. The results represented adenocarcinoma in 137 (84.6)cases and mucinous subtype in 23 (14.19) cases. The three most common sites of metastasis were the liver (99, 61.1), peritoneum (67, 41.3), and lung (33, 20.3). In the first line, allpatients received bi-chemotherapy plus bevacizumab, i.e., fluorouracil, oxaliplatin, and leucovorin in 34 (20.9%) patients; capecitabine plus oxaliplatin in 88 (54.3%) patients; leucovorin, fluorouracil, and irinotecan in 17 (10.4%) patients; andcapecitabine plusirinotecan in 23 (14.1%) patients. Response after first-line treatment was progression in 74 (45.7) cases, stability in 42 (25.9) cases, partial response in 35(21.6) cases, and complete response in 11 (6.8) cases. Nine (6%) patients were able to benefit from surgical resection of metastatic lesions. Overall, 77 (47%)patients received second-line chemotherapy, i.e., 5-FU with irinotecan in 40 (51.8%)cases or with oxaliplatin in 30(38.8%) cases. Two patients developed undesirable side effects under bevacizumab (hypertension). The median progression-free survival and median overall survival of the study cohort were 9 months and 14 months, respectively. Nevertheless, patients who underwent primary tumor resection (p = 0.048), those with right‑sided tumors (p = 0.022), those who received a higher number of treatment cycles (p = 0.020), and those who received maintenance treatment (p = 0.001) had a longer median overall survival. Conclusions Chemotherapy combination with bevacizumab is considered as the cornerstone of metastatic colorectal cancer treatment in our region. With the new healthcare and social security systems, easier access to expensive treatments and molecular pathology tests is currently available. It is important to highlight that real-world data can offer valuable insights into the daily clinical practice of medical oncology.

Reduced chemokine C-C motif ligand 1 expression may negatively regulate colorectal cancer progression at liver metastatic sites.

Colorectal cancer (CRC) liver metastasis, albeit a stage-IV disease, is completely curable by surgical resection in selected patients. In addressing the molecular basics of this phenomenon, differentially expressed genes at primary and liver metastatic sites were screened by RNA sequencing with the use of paraffin-embedded surgical specimens. Chemokine C-C motif ligand 1 (CCL1), a chemotactic factor for a ligand of the chemokine C-C motif receptor 8 (CCR8), was isolated as one of the differentially expressed genes. Histological analysis revealed that the number of CCL1-positive cells, mainly tumour associated macrophages (TAMs) located in the stroma of CRC, decreased significantly at liver metastatic sites, while the expression level of CCR8 on CRC remained unchanged. To explore the biological significance of the CCL1-CCR8 axis in CRC, CCR8-positive CRC cell line Colo320DM was used to assess the effect of the CCL1-CCR8 axis on major signalling pathways, epithelial mesenchymal transition induction and cell motility. Upon stimulation of recombinant CCL1 (rCCL1), phosphorylation of AKT was observed in Colo320DM cells; on the other hand, the corresponding significant increase in MMP-2 levels demonstrated by RT-qPCR was nullified by siRNA (siCCR8). In the scratch test, rCCL1 treatment significantly increased the motility of Colo320DM cells, which was similarly nullified by siCCR8. Thus, the activation of the CCL1-CCR8 axis is a positive regulator of CRC tumour progression. Reduced CCL1 expression of TAMs at liver metastatic sites may partly explain the unique slow tumour progression of CRC, thus providing for a grace period for radical resection of metastatic lesions.

Supraorbital Eyebrow Approach for Translamina Terminalis Resection of Third Ventricle Metastasis: 2-Dimensional Operative Video.

Tumors involving the third ventricle are rare, accounting for 0.6%-0.9% of all brain tumors. This deep-seated cavity is surrounded by critical neurovascular structures, making safe surgical resection of lesions in this region challenging. Traditionally, tumors of the third ventricle have been approached through a craniotomy and microsurgical resection.1-4 The supraorbital keyhole approach is a minimally invasive technique that can be used with minimal retraction of the brain and limited craniotomy while establishing a surgical field comparable with what can be achieved using traditional transcranial approaches. In this video, we describe the case of a 54-year-old man who underwent a supraorbital eyebrow approach for translamina terminalis resection of papillary thyroid carcinoma metastasis to the third ventricle. A gross total resection was achieved. The results achieved in our series are comparable with previously published reports of patients who underwent surgical resection of metastatic lesions involving the third ventricle.5-11 The patient consented to the procedure and to the publication of his image.

Impact of Complete Surgical Resection of Metastatic Lesions in Patients with Advanced Renal Cell Carcinoma in the Era of Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors.

Complete metastasectomy (CM) in metastatic renal cell carcinoma (mRCC) has demonstrated efficacy in the cytokine era, but its effectiveness in the era of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) remains unclear. A multi-institutional database included clinicopathological data of 367 patients with mRCC. Patients were divided into two groups: the CM group and the non-CM group. These two groups were compared before and after propensity score matching (PSM). Cox proportional hazard models were used to detect factors associated with disease-free survival (DFS) and overall survival (OS) from mRCC diagnosis. The CM group showed a significant association with longer overall survival compared to the non-CM group in the PSM-unadjusted cohorts (p < 0.001, hazard ratio 0.49, 95% confidence interval 0.35-0.69), but no superiority was noted in the adjusted cohorts. The median DFS after CM was 24 months, with no significant differences based on relapse timing. Notably, the international metastatic RCC database consortium risk categories and metastatic burden were associated with DFS. This study supports the potential of CM in mRCC management during the TKI/ICI era, although limitations including sample size and selection bias need to be considered.

Role of Immunotherapy in Renal Cell Carcinoma; A Case Study

Introduction: The most common cancer of kidney is- renal cell carcinoma. Early diagnosis can make a hope from the recovery of the disease. The incidence of renal cell carcinoma is commonly found in elderly aged patients. Sometimes it occurs in one kidney whereas, sometimes it effects both kidneys. Smoking, overweight, taking excessive painkillers can increase the chance of renal cell carcinoma. Case Presentation: A 57 years old Bangladeshi diabetic male patient, was diagnosed as right sided renal cell carcinoma (stage pT3cN0G2) along with the chief complaint of recurrent gross hematuria came to outdoor in April 2020. After confirmed diagnosis surgery had done followed by medications. From 10/03/2022, patient started 1 cycle of oral therapy with tablet Sunitinib. After that, immunotherapy and targeted therapy were advised to start with injection Pembrolizumab 200mg every three weeks followed by tablet Axitinib 5mg for every two weeks. Patient received 17 cycles of Pembrolizumab followed by Axitinib and got the last cycle at 24/02/2024. Conclusion: With the minimal side effects, it is evident that, Pembrolizumab has shown a positive response to the patient. It has added the new standard care of treatment of renal cell carcinoma at intermediate-high or high risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions.

Development of an Algorithm to Predict Recurrences After Resection of Liver Metastases in Patients With Metastatic Colorectal Cancer.

Hepatic recurrences after resection of metastatic lesions in advanced colorectal cancer (CRC) have an enormous impact on patient prognosis. Response evaluation criteria in solid tumor (RECIST) or morphologic response on computed tomography (CT) have been reported as surrogate prognostication markers. This study assessed a novel algorithm for the prognostication of liver metastasis treatment. Forty-seven patients with liver metastases from CRC who underwent liver resection after systemic chemotherapy were included. The CT values examined before and after chemotherapy were collected. The velocity of CT values (CTvΔ) was calculated, and the subjects were divided into CTvΔ_high and _low groups. Clinicopathological variables, recurrence-free survival (RFS), and overall survival (OS) were statistically compared between the two groups. In addition, the effect of the combined evaluation of CTvΔ and carcinoembryonic antigen (CEA) was evaluated. In univariate analyses, the hazard ratio (HR) for a recurrence after liver resection was relatively higher in the RECIST_stable disease (SD) or _progressive disease (PD) and the CTvΔ_low groups. In multivariate analysis, the HR was significantly higher in the CEA_high, the RECIST_SD or PD, and the CTvΔ_low groups. The RFS was significantly longer in the CTvΔ_high group. Furthermore, the combination of CTvΔ and CEA predicted the RFS and OS. Our algorithm using CTvΔ could be a useful tool to select patients suitable for liver resection of hepatic CRC metastases.

Pulmonary benign metastasizing leiomyoma in patients aged 45 years and younger: clinical features and novelty in treatment

BackgroundPulmonary benign metastasizing leiomyoma (PBML) is the most common extrauterine spread of uterine leiomyoma, and its biological behavior is traditionally thought to be hormone dependent. Studies on older PBML patients have been previously reported, but limited literature has been published regarding the clinical features and treatment of PBML in young women.MethodsA total of 65 cases of PBML in women aged 45 years and younger were reviewed, including 56 cases selected from PubMed and 9 cases from our hospital. The clinical characteristics and management of these patients were analyzed.ResultsThe median age of all the patients at diagnosis was 39.0 years. PBML most commonly presented as bilateral solid lesions (60.9%), with other rare imaging manifestations. The median interval time from a pertinent gynecologic procedure to diagnosis was 6.0 years. A total of 16.7% of patients received careful observation, and all achieved stable status in a median follow-up time of 18.0 months. A total of 71.4% of patients were administered anti-estrogen therapies, including surgical castration (33.3%), gonadotropin-releasing hormone analog (23.8%) and anti-estrogen drugs (14.3%). Eight of 42 patients underwent surgical resection of metastatic lesions. Patients who underwent curative surgery for the removal of pulmonary lesions combined with adjuvant anti-estrogen therapies had favorable outcomes compared with those who only underwent surgical resection. The disease control rates of surgical castration, gonadotropin-releasing hormone analog, and anti-estrogen drugs were 85.7%, 90.0%, and 50.0%, respectively. For two patients, sirolimus (rapamycin) achieved successful relief of symptoms and control of pulmonary lesions without lowering hormone levels and causing estrogen deficiency symptoms.ConclusionsIn the absence of standard treatment guidelines for PBML, maintaining a low-estrogen environment using different kinds of antiestrogen therapies has been the mainstream strategy and has satisfying curative effects. A wait-and-see strategy might be an option, but therapeutic approaches must be contemplated when complications or symptoms progress. For PBML in young women, the negative effect on ovarian function of anti-estrogen treatment, especially surgical castration, should be considered. Sirolimus might be a new treatment option for young PBML patients, especially for those who want to preserve ovarian function.

Role of lymphadenectomy during primary surgery for kidney cancer.

Lymph node dissection (LND) during radical nephrectomy (RN) for renal cell carcinoma (RCC) is not considered as a standard. The emergence of robot-assisted surgery and effective immune checkpoint inhibitors (ICI) in recent years may change this and lymph node (LN) staging has become easier and has a clinical impact. In this review, we aimed to reconsider the role of LND today. Although the extent of LND has still not been well established, removal of more LN seems to provide better oncologic outcomes for a select group of patients with high-risk factors such as clinical T3-4. Adjuvant therapy using pembrolizumab has been shown to improve disease free survival if complete resection of metastatic lesions as well as the primary site is obtained in combination. Robot assisted RN for localized RCC has been widespread and the studies regarding LND for RCC has been recently appeared. The staging and surgical benefits and its extent of LND during RN for RCC remains unclear, but it is becoming increasingly important. Technologies that allow an easier LND and adjuvant ICI that improve survival in LN-positive patients are engaging the role of LND, a procedure that was needed, but almost never done, is now indicated sometimes. Now, the goal is to identify the clinical and molecular imaging tools that can help identify with sufficient accuracy who needs a LND and which LNs to remove in a targeted personalized approach.

Phase 3 LITESPARK-022: Pembrolizumab (pembro) plus hypoxia-inducible factor 2α (HIF-2α) inhibitor belzutifan as adjuvant treatment for clear cell renal cell carcinoma (ccRCC).

TPS748 Background: Treatment with the PD-1 inhibitor pembro produced significant improvement in disease-free survival after surgery for patients (pts) with ccRCC in the phase 3 KEYNOTE-564 trial. Based on these results, pembro was approved by the US Food and Drug Administration and the European Medicines Agency for adjuvant treatment of pts with RCC at increased risk of recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions. Despite advances in the treatment landscape for RCC, more effective adjuvant treatment strategies are needed for pts at risk of recurrence after surgery. HIF-2α is an established oncogenic driver in ccRCC, and promising antitumor activity in advanced ccRCC and von Hippel-Lindau disease–associated RCC has been demonstrated with the HIF-2α inhibitor belzutifan. The multicenter, double-blind, randomized, phase 3 LITESPARK-022 study (NCT05239728) will evaluate the efficacy and safety of pembro plus belzutifan compared with placebo plus pembro as adjuvant treatment following nephrectomy in pts with ccRCC. Methods: Key eligibility criteria include adults with histologically or cytologically confirmed intermediate-high risk, high risk, or M1 with no evidence of disease (NED) RCC with a clear cell component; pts with no prior systemic therapy, nephrectomy, and/or metastasectomy ≤12 weeks before randomization; and pts who are tumor free per computed tomography/magnetic resonance imaging. Approximately 1600 pts will be randomly assigned to receive belzutifan 120 mg orally once daily plus pembro 400 mg intravenously (IV) every 6 weeks (Q6W) for ≤9 administrations (~54 weeks) or oral placebo plus pembro 400 mg IV Q6W for ≤9 administrations (~54 weeks) or until verified disease recurrence by blinded independent central review, start of new anticancer treatment, unacceptable toxicity, or decision to withdraw. Stratification factors are tumor grade (1 or 2 vs 3 or 4) and risk type (intermediate-high risk versus high risk versus M1 NED). Pts will be radiologically evaluated Q12W from randomization through year 2, Q16W in years 3 to 5, and Q24W in years 6 and beyond. Adverse events will be monitored throughout the study and for 30 days following cessation of study treatment (90 days for serious adverse events). The primary end point is disease-free survival. Secondary end points include overall survival, safety, disease recurrence–specific survival, and patient-reported outcomes. Recruitment is underway in Asia, Australia, Europe, North America, and South America. © 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved. Clinical trial information: NCT05239728 .

Pembrolizumab (Keytruda)

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class. The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec. This review assesses pembrolizumab (Keytruda), supplied as: powder for solution for infusion: 50 mg lyophilized powder of pembrolizumab in a single-use vial, for reconstitution solution for infusion: 100 mg/4 mL (25 mg/mL) solution in a single-use vial administered as an IV infusion over 30 minutes. Indication: Adjuvant treatment of adult patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Pembrolizumab (Keytruda)

&#x0D; CADTH recommends that Keytruda should be reimbursed by public drug plans for the adjuvant treatment of adult patients with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions if certain conditions are met.&#x0D; Keytruda should only be covered to treat patients aged 18 years and older with RCC of clear cell subtype and previous nephrectomy, with or without surgery to remove 1 or more metastases, who are at intermediate-high or high risk of the tumour returning, and without prior systemic therapy for advanced RCC. Patients should also be in relatively good health.&#x0D; Keytruda should only be reimbursed if prescribed by a clinician with experience in RCC management, in specialized clinics with expertise in systemic treatment and immunotherapy delivery, and if the price of Keytruda is reduced. Keytruda should not be used in combination with other adjuvant cancer treatments.&#x0D;

LITESPARK-022: A phase 3 study of pembrolizumab + belzutifan as adjuvant treatment of clear cell renal cell carcinoma (ccRCC).

TPS4602 Background: Patients with locally advanced renal cell carcinoma (RCC) may experience recurrence after surgery. In the phase 3 KEYNOTE-564 (NCT03142334) trial, adjuvant pembrolizumab demonstrated significant improvement in disease-free survival (DFS) in ccRCC, leading to FDA approval of pembrolizumab (November 17, 2021) for adjuvant treatment of patients with RCC at intermediate-high or high risk for recurrence following nephrectomy or following nephrectomy and resection of metastatic lesions. Despite benefit of pembrolizumab, there is an unmet need for more effective adjuvant treatment for patients at risk for recurrence after definitive surgery. The HIF-2α inhibitor belzutifan (MK-6482) has shown activity and good tolerability in patients with advanced ccRCC and von Hippel-Lindau (VHL) disease–associated RCC. Combining belzutifan with pembrolizumab may be a therapeutic option as adjuvant treatment of ccRCC. This global, multicenter, double-blind, randomized, phase 3 study LITESPARK-022 (NCT05239728) is designed to compare the efficacy and safety of belzutifan + pembrolizumab with that of placebo + pembrolizumab as adjuvant treatment of ccRCC after nephrectomy. Methods: Approximately 1600 patients with histologically or cytologically confirmed RCC (intermediate-high [pT2, grade 4 or sarcomatoid, N0, M0 or pT3, any grade, N0, M0], high [pT4, any grade, N0, M0 or pT, any stage/grade, N+, M0] or M1 NED [patients who present with the primary kidney tumor and solid, isolated, soft tissue metastases that can be resected at the time of nephrectomy or ≤2 years from nephrectomy) with a clear cell component and had not previously received systemic therapy will be enrolled. Patients must have undergone nephrectomy and/or metastasectomy ≤12 weeks before randomization and be tumor free, confirmed by CT/MRI. Stratification factors are tumor grade (1 or 2 vs 3 or 4) and risk type (intermediate-high vs high vs M1 NED). Patients will be randomly assigned 1:1 to receive belzutifan 120 mg orally once daily + pembrolizumab 400 mg IV every 6 weeks (Q6W) or oral placebo + pembrolizumab 400 mg IV Q6W. Pembrolizumab treatment will be administered for up to 9 doses (̃1 year); belzutifan and placebo may be continued for a maximum of 54 weeks. Disease recurrence will be evaluated radiologically Q12W from randomization through year 2, Q16W in years 3-5, and Q24W in years 6 and beyond. Adverse events (AEs) will be monitored by NCI CTCAE v5.0 through 30 days (90 days for serious AEs) after cessation of study drug. The primary end point is DFS, as assessed by investigator, defined as time from randomization to first documented event of local recurrence, occurrence of distant kidney cancer metastasis, or death from any cause, whichever occurs first. The key secondary end point is overall survival. Other secondary end points are safety, disease recurrence–specific survival and patient-reported outcomes. Clinical trial information: NCT05239728.

Adjuvant pembrolizumab for postnephrectomy renal cell carcinoma (RCC): Expanded efficacy analyses from KEYNOTE-564.

4512 Background: The randomized, double-blind, phase 3 KEYNOTE-564 study (NCT03142334) met its primary end point of disease-free survival with adjuvant pembrolizumab versus placebo after nephrectomy in patients with localized RCC who are at increased risk for recurrence. Extended follow-up (30-month median follow-up) continued to support the benefit of adjuvant pembrolizumab. We describe additional efficacy analyses of time to first subsequent drug treatment or any-cause death (TFST) and time from randomization to progression on next line of therapy or any-cause death (PFS2). Methods: Patients with histologically confirmed clear cell RCC, with intermediate-high or high risk for recurrence (pT2, grade 4 or sarcomatoid, N0, M0; or pT3-4, any grade, N0 M0; or pT any stage, any grade, N+ M0) after nephrectomy, or after nephrectomy and resection of metastatic lesions (M1 NED), were randomly assigned 1:1 to receive pembrolizumab 200 mg IV or placebo Q3W for up to 17 cycles (̃1 y). Exploratory analyses of TFST and PFS2 were conducted. The Kaplan-Meier method was used to estimate TFST and PFS2. Hazard ratios (HRs) were estimated using a Cox regression model. Results: Of 994 patients, 496 were randomly assigned to receive pembrolizumab and 498 to placebo. Median time from randomization to the data cutoff date (June 14, 2021) was 30.1 months (range, 20.8-47.5). Overall, 67 patients (13.5%) in the pembrolizumab group and 99 patients (19.9%) in the placebo group received ≥1 line of subsequent anticancer drug therapy. Of patients who received ≥1 line of subsequent drug therapy, most in the pembrolizumab group (90.0% [60/67]) and placebo group (85.9% [85/99]) received a VEGF/VEGFR-targeted therapy; 23.9% of patients (16/67) in the pembrolizumab group and 59.6% (59/99) in the placebo group received an anti–PD-1/PD-L1 agent. Seventy-seven TFST events were observed in the pembrolizumab group; 110, in the placebo group. Compared with placebo, adjuvant treatment with pembrolizumab delayed TFST (HR, 0.67; 95% CI, 0.50-0.90; medians not reached). A total of 108 PFS2 events were observed, 40 (8.1%; 12 death events and 28 progression events) in the pembrolizumab group and 68 (13.7%; 14 death events and 54 progression events) in the placebo group. PFS2 was also delayed with pembrolizumab compared with placebo (HR, 0.57; 95% CI, 0.39-0.85; medians not reached). Conclusions: Treatment with adjuvant pembrolizumab reduced risk for TFST and PFS2 compared with placebo. Results of this exploratory analyses suggest sustained clinical benefit of adjuvant pembrolizumab and support the use of adjuvant pembrolizumab after nephrectomy as standard of care for patients with localized RCC at increased risk for recurrence. Clinical trial information: NCT03142334.

Can surgical resection of metastatic lesions be beneficial to pancreatic ductal adenocarcinoma patients with isolated lung metastasis?

Won-Gun YUN, Wooil KWON, Youngmin HAN, Hee Ju SOHN, Jae Seung KANG, Yoon Hyung KANG, Hyeong Seok KIM, Mirang LEE, Hongbeom KIM, Alexander THOMAS, Michael KLUGER, Jin-Young JANG*. Ann Hepatobiliary Pancreat Surg 2022;26:S114. https://doi.org/10.14701/ahbps.2022S1.OP-8-5

Can Surgical Resection of Metastatic Lesions Be Beneficial to Pancreatic Ductal Adenocarcinoma Patients with Isolated Lung Metastasis?

Simple SummaryWith the development of chemotherapy, studies have been conducted on the possibility of conversion surgery in metastatic pancreatic ductal adenocarcinoma (PDAC) patients. In addition, studies with large-scale public data have reported that patients with isolated lung metastasis have a good prognosis and can benefit from survival through surgical treatment. Our study aims to evaluate the effect of metastatectomy and prognostic factors in PDAC patients with isolated lung metastasis by analyzing the data from 1342 patients in our institution. We showed that PDAC patients with isolated lung metastasis who underwent metastatectomy seemed to have better survival when compared with patients who underwent only chemotherapy or supportive care. In addition, we performed the analysis using the National Cancer Database for external validation purposes and found consistent results compared to our analysis. Our findings suggest that PDAC patients with isolated lung metastasis should be considered for multimodal therapy with chemotherapy and surgical treatment.In the era of effective chemotherapy on pancreatic ductal adenocarcinoma (PDAC) with distant metastasis, data on the effects of metastatectomy are lacking. So, we investigated the effect of metastatectomy on survival after metastasis in PDAC patients with isolated lung metastasis. This retrospective study analyzed 1342 patients who were histologically diagnosed with PDAC with distant metastasis from January 2007 to December 2018, of which 83 patients had isolated pulmonary metastasis. Additionally, 4263 patients were extracted from the National Cancer Database (NCDB) and analyzed. Log-rank test and Kaplan−Meier survival analysis were used to analyze survival after metastasis. The five-year survival rate was significantly higher in patients who underwent pulmonary metastatectomy than in those who received only chemotherapy or supportive treatment (60.6% vs. 6.2% vs. 0.0%, p < 0.001). A similar trend was observed in the NCDB (two-year survival rate, 27.4% vs. 15.8% vs. 4.7%, p < 0.001). In the multivariate analysis, lung lesion multiplicity (hazard ratio (HR) = 2.004, p = 0.017), metastatectomy (HR = 0.278, p = 0.036), chemotherapy (HR = 0.434, p = 0.024), and chemotherapy cycles (HR = 0.300, p < 0.001) had significant effects on survival. Metastatectomy with primary pancreatic lesions is recommended with effective chemotherapy in PDAC patients with isolated lung metastasis.

Pembrolizumab as post nephrectomy adjuvant therapy for patients with renal cell carcinoma: Results from 30-month follow-up of KEYNOTE-564.

290 Background: The double-blind, multicenter, randomized KEYNOTE-564 study (NCT03142334) is the first positive phase 3 study of adjuvant immunotherapy for patients (pts) with renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence after nephrectomy or nephrectomy and resection of metastatic lesions. Adjuvant pembrolizumab resulted in a statistically significant improvement in disease-free survival (DFS) vs placebo with 24 months of follow-up (HR 0.68, 95% CI 0.53−0.87; P = 0.0010 [one-sided]). We present updated efficacy and safety results from KEYNOTE-564 with 6 months of additional follow-up. Methods: Pts had histologically confirmed, clear cell RCC (pT2, grade 4 or sarcomatoid, N0 M0; pT3 or pT4, any grade, N0 M0; any pT, any grade, N+ M0; or M1 NED [no evidence of disease after primary tumor and soft tissue metastases completely resected ≤1 year from nephrectomy]) and had undergone surgery ≤12 weeks prior to randomization. The primary endpoint was DFS by investigator assessment in all randomized pts (ITT population). Overall survival (OS) was a key secondary endpoint. Safety/tolerability in all treated pts was a secondary endpoint. Results: 994 pts were randomized 1:1 to pembrolizumab (N = 496) or placebo (N = 498). As of data cutoff date of June 14, 2021, median (range) follow-up, defined as time from randomization to data cutoff, was 30.1 (20.8−47.5) months. In this updated analysis, DFS benefit with pembrolizumab was maintained (HR 0.63, 95% CI 0.50−0.80; nominal P &lt; 0.0001) and was consistent across subgroups, including pts with M0 disease with intermediate-high risk of recurrence (HR 0.68, 95% CI 0.52−0.89), M0 high risk of recurrence (HR 0.60, 95% CI 0.33−1.10), or M1 NED (HR 0.28, 95% CI 0.12−0.66). The estimated DFS rate at 24 months was 78.3% with pembrolizumab vs 67.3% with placebo. A total of 66 OS events were observed, 23 in the pembrolizumab arm and 43 in the placebo arm (HR 0.52, 95% CI 0.31−0.86; P = 0.0048); the p-value did not cross the statistical hypothesis testing boundary and additional follow-up is planned for this key secondary endpoint. The estimated OS rate at 24 months was 96.2% with pembrolizumab vs 93.8% with placebo. With additional follow-up, no increase in any-grade or grade 3-4 adverse events, or steroid use for immune-mediated adverse events was observed. No deaths related to pembrolizumab occurred. Conclusions: At 30 months of follow-up, adjuvant pembrolizumab continued to demonstrate a consistent and clinically meaningful improvement in DFS vs placebo in pts with RCC at high risk of recurrence. No new safety signals were observed with pembrolizumab in the adjuvant setting. Clinical trial information: NCT03142334.

Successful Surgical Resection and Chemotherapy for Unresectable Hepatoblastoma With Pulmonary Metastases and for Lung Recurrence After Liver Transplantation: A Case Report

Liver transplantation (LTx) is indicated for unresectable hepatoblastoma (HB) without distal metastasis. However, to our knowledge, there is no consensus on the management of unresectable HB with pulmonary metastases, or on the treatment of recurrent HB. We report a successful case of metastatic HB treated with repeated lung resection, chemotherapy, and LTx. This study strictly complied with the Helsinki Congress and the Istanbul Declaration regarding donor source. Our case was a 1-year-old boy who developed pre-treatment extent of disease (PRETEXT) Ⅲ HB with multiple pulmonary metastases. The liver tumor was unresectable because it involved all hepatic veins. After 3 cycles of chemotherapy (cisplatin/carboplatin plus doxorubicin), the remaining 2 pulmonary metastases were resected and living donor liver transplantation (LDLT) was performed. Five months after LDLT, a tumor recurrence was detected in the right lung. Repeat lung resection was performed followed by 1 cycle of chemotherapy (carboplatin plus doxorubicin). There has been no recurrence for 18 months since the last lung resection. Previous reports revealed that 14 patients, including the present case, underwent LTx after resection of metastatic HB pulmonary lesions. Of these patients, the 2-year survival rate after LTx was 91%. Recurrence was reported in 5 patients, 2 of whom were successfully treated with repeated resection of the metastatic lesions. LTx after resection of lung recurrence may be a potential treatment for unresectable HB with pulmonary metastases.