Free Survival Rate Research Articles

Multicenter randomized phase II study of short course FOLFOX + nivolumab (Nivo) followed by maintenance Nivo +/- radiation (RT) in the first line treatment of metastatic or unresectable gastroesophageal adenocarcinoma (mGEA).

4060 Background: Standard 1L treatment of mGEA is chemotherapy with checkpoint inhibition (CPI). However, prolonged cytotoxic therapy can impair CPI efficacy by reducing effective immune infiltration over time. Alternatively, radiotherapy (RT) can augment CPI efficacy in multiple malignancies. In this randomized phase II multicenter study, we examined short course chemotherapy and the potential of RT in improving the efficacy of CPI. Methods: This was a multicenter study of FOLFOX + Nivo for 3 months followed by maintenance Nivo with or without RT (20Gy in 5 fractions to the dominant lesion). Eligible patients had adequate end organ function, measurable disease, and were CPI candidates, regardless of PD-L1 CPS expression. Patients without progression at 2 months were randomized 1:1 to Nivo or Nivo + RT. The primary objective was to demonstrate that adding RT to Nivo in the maintenance setting improved efficacy as measured by 12-month progression free survival (PFS) rate. A secondary objective was to demonstrate that the efficacy of short course chemo is similar to continuing FOLFOX until progression (from CM649, 12-mo PFS 34% [95% CI: 30-38%] all pts). Results: Seventy-three evaluable pts enrolled from 7/11/2019 to 4/13/2023. Mean age 63.1, M:F 2.7:1. PD-L1 distribution: CPS > 5 in n=37 (50.7%), CPS 1-4 16 (22%), CPS <1 20 (27.4%). Seven (9.6%) patients progressed at 2 months and had a median OS of 90d (95%CI 44-178d). The remaining 66 patients were randomly assigned to Nivo maintenance (n=32), or Nivo + RT (n=34). The objective response rate for all evaluable pts is 43.8% (95%CI 32.5-55.2%). The 12-month and median PFS for all evaluable pts (n=73) is 29.5% (19.2- 40.7%) and 7.4 mo (5.7-8.6mo); for Nivo alone 34.4% (18.8- 50.6%) and 7.5mo (5.4-14.2mo), and Nivo + RT 30.0% (14.9-46.8%) and 7.8 mo (5.7-9.6mo) respectively (p=NS). The 12-month and median OS for all evaluable pts (n=73) is 60.9% (48.6-71.1%) and 16mo (10.8-22.4mo); for Nivo alone 71.9% (52.9- 84.3%) and 22.4mo (13.2-NAmo), and Nivo + RT 62.8% (43.7-76.9%) and 17.9 mo (10.3-24.5mo) respectively (p=NS). Forty-nine patients progressed after randomization, of which 30 patients were rechallenged with FOLFOX or CAPOX with continued response – median time to 2nd progression 3.93mo (range 0.5-15.2mo). Amongst patients who were rechallenged with oxaliplatin based therapy, the median time to oxaliplatin failure was 13.76 mo (range 4.4–30mo). Conclusions: Short course FOLFOX + Nivo followed by maintenance Nivo has a similar progression free and overall survival to continuing FOLFOX + Nivo until progression. Patients who receive short course chemotherapy can successfully be rechallenged with oxaliplatin. The addition of RT to maintenance Nivo does not improve CPI efficacy. Short course FOLFOX with CPI is a safe and effective 1L option for mGEA. Clinical trial information: NCT04021108 .

A phase 2, single arm, European multi-center trial evaluating the efficacy of afatinib as first line or later line treatment in advanced chordoma.

11517 Background: EGFR and Her2 overexpression in chordoma is well known, and chordoma cell-lines and mouse models were proven to be sensitive to EGFR inhibitor afatinib. This phase 2, single arm, European multi-center trial was designed to evaluate the efficacy of afatinib as first- or later-line tyrosine kinase inhibitor (TKI) treatment in advanced chordoma. Here we report efficacy and safety data. Methods: Eligible patients (pts) had locally advanced or metastatic, pathologically proven, EGFR expressing chordoma, not amenable for local therapies, with confirmed measurable and progressive lesions according to RECIST1.1. Pts were treated with afatinib 40mg/day in a 4 week cycle until disease progression (PD), unacceptable toxicity or withdrawal. Radiological tumor response assessment was performed every 3 cycles. The primary endpoint was response defined as progression free survival (PFS) rate ≥12 months (mos) for first-line cohort 1 and ≥ 9 mos for further-line treatment cohort 2, and change from baseline in EORTC QLQ- C30 and Brief pain inventory (BPI) questionnaires. Pts were enrolled using a Simon’s two-stage design, enrolling 13 patients in stage one, ≥3 patients with a PFS ≥ 12 or 9 mos were needed to enter stage two, where 43 pts total were to be enrolled, and ≥13 free from progression at 9 or 12 mos were required to meet the primary endpoint for success. Results: From Jun 2018 to Oct 2022, 47 pts were included. Four were ineligible for efficacy analysis (1 withdrawal, 3 stopped due to toxicity before first radiological evaluation). 34 entered cohort 1, 13 cohort 2. 31 (66.0%) were men, median age was 53 (range 28-85) years. 16 (34.0%) pts received prior systemic therapy (3 chemotherapy, 13 TKI, 2 immunotherapy, 2 other). The PFS rate at 12 mos was 40.0% in cohort 1 (12/30 pts), and 38.5% in cohort 2 (5/13 pts). Overall median PFS was 8.6 mos (95% CI 5.6-13.6); 9.1 mos (95% CI 5.8-16.6) in cohort 1 and 7.1 mos (95% CI 2.8-16.5) in cohort 2. Two pts remained on treatment at time of analysis. Best objective response by RECIST 1.1 was partial response in 4 pts (9.3%), stable disease in 33 (76.7%), PD in 5 pts (11.6%) and 1 (2.3%) unknown due to clinical progression. Median follow-up time was 23.7 mos (interquartile range 11.0-21.2). 16/47 pts (30.4%) experienced grade ≥3 adverse events (AEs). No grade 5 AEs related to afatinib were reported. Most common grade 3-4 afatinib-related AEs were skin toxicity (10.6% of pts), diarrhea (10.6%), mucositis (6.4%), hypertension (4.3%). Dose reduction was needed in 20/47 (42.6%) pts, and at least one dose interruption was needed in 31/47 (66.0%) pts. Conclusions: With a PFS rate at 12 mos of 40.0% in the first-line cohort and 38.5% at 9 mos in the further-line cohort, this phase 2 study met the PFS endpoint. QoLQ data will be provided at the conference . Partial response by RECIST was seen in 4/43 pts. Toxicity and dose reductions were relevant but manageable in most pts. Clinical trial information: NCT03083678 .

A randomized phase II trial of 8 months of afatinib switching to osimertinib (A) versus osimertinib alone (B) as first-line treatment in advanced NSCLC patients with common EGFR mutation: YAMATO study (TORG1939/WJOG12919L).

8574 Background: NSCLC with common EGFR mutation (L858R or exon 19 deletion (Del19)) is known to originally comprise small portion of uncommon and compound EGFR variant cells including T790M-mutant ones albeit treatment-naïve. To overcome concomitant heterogeneous EGFR mutations, we planned a randomized phase II trial to assess the strategy of switching to osimertinib following 8 months of afatinib compared with osimertinib alone. Methods: YAMATO study is an open-label, multi-center, randomized phase II study. Patients with newly diagnosed stage III/IV/recurrent NSCLC harboring EGFR activating mutations (L858R or Del19) were randomized in a 1:1 ratio to receive up-front 8 months of afatinib (30 mg or 40 mg QD) followed by osimertinib (80 mg QD) (arm A) or osimertinib (80mg QD) alone (arm B) until disease progression or intolerable toxicity. The primary endpoint is 2-year progression free survival (PFS) rate with threshold rate of 22% and expected rate of 40% (one-tailed alpha of 0.1, beta of 0.2). Secondary endpoints are objective response rate (ORR), PFS, time to treatment failure, overall survival and adverse events. Results: Between May 2020 and Apr 2021, 113 patients were enrolled from 27 institutions (A/B 56/57). Patient characteristics were as follows: median ages, 73.5/71 years (range 41-85/41-92 years); proportion of males, 42.9/35.1%; EGFR mutation types, L858R/Del19 59/41% in A, 58/42% in B. The difference of two-year PFS rate was not observed statistically significant between groups (37.3% [80% CI, 29.0 to 45.5] in arm A vs 47.4% [80% CI, 38.5 to 55.7] in arm B; p=0.44; HR:1.28 [80% CI, 0.95-1.73]). The ORR was 82% in arm A and 87% in arm B. With the median follow-up of 27.5 months, median PFS was 16.8 months in arm A, and 22.2 months in arm B (HR: 1.280, p = 0.29). Severe pneumonitis occurred in 7% in arm A, most of which developed after switching to osimertinib, and 1.8% in arm B. Conclusions: YAMATO study failed to demonstrate the superiority of EGFR-TKI switching therapy of 8 months afatinib to osimertinib over osimertinib alone in terms of 2-year PFS rate in untreated advanced NSCLC patients with common EGFR mutations. Clinical trial information: 031200021 .

First results of the NOGGO PERCEPTION: Phase II investigational study of pembrolizumab in combination with chemotherapy in platinum-sensitive recurrent low-grade serous ovarian cancer.

e17550 Background: Low-grade serous ovarian cancer (LGSOC), a rare ovarian malignancy, exhibits a very limited responsiveness to chemotherapy. There is a pressing need for new therapeutic combinations with modern agents to enhance response rates and prognosis in this patient subgroup. Immune checkpoint inhibitors offer a promising pathway, having shown effectiveness in various malignant diseases, including selected cases of ovarian cancer. If our trial should show pembrolizumab effectivity in LGSOC, it would be a signal and impulse for future clinical studies in this rare disease. Methods: This clinical trial is a multi-center, single-arm phase 2 study to evaluate pembrolizumab therapy concomitant to platinum-based chemotherapy (carboplatin plus pegylated liposomal doxorubicin & carboplatin plus gemcitabine) and as maintenance in recurrent LGSOC cases. Eligible for the trial are LGSOC patients with progression or recurrence at least six months after most previous platinum-containing therapy and in good general performance (ECOG 0/1). The primary objective is the 12 months progression free survival (PFS) rate. Secondary end-points include overall survival, response rate (RR), PFS and RR according to Ki67 expression levels, time to first subsequent therapy and its response, safety and quality of life. The trial is planned according to Simon’s two-stage design with total sample size up to 33 patients. The null hypothesis is PFS-rate of at least 12 months of 20%. During the first stage 18 patients were enrolled and since 5 patients showed PFS of 12 months the study has been continued within stage 2 to enrol additional 15 patients. The trial can be claimed as successful, if at least 11 patients show PFS after 12 months. Assuming a true PFS-rate of 40%, this trial has 5% type I error rate and 80% power. Results: Data from 18 patients enrolled into this trial from FPI up to the time of interim analysis have been analyzed. 5 patients had reached the primary endpoint. 6 patients progressed or died before they reached the primary endpoint. At this time, 10 patients are still undergoing treatment and 7 patients may still reach the primary endpoint. Patients have a median age of 60 years (range: 43-81), ECOG score of 0 was recorded in 16 patients (88.9%) and most received one prior line of chemotherapy (61.1%, range: 1-5). 14 patients (77.8%) received carboplatin + PLD and 4 patients (22.2%) received carboplatin + gemcitabine as chemotherapy. 10 patients (55.6%) had at least one SAE. 3 patients (16.7%) had at least one SAE with relation to study treatment. 1 SAE resulted in a fatal outcome but was assessed not be related to study treatment. Conclusions: The interim analysis showed positive results, strengthening the hypothesis that pembrolizumab is an effective agent capable of extending progression-free survival in the studied patient population. Clinical trial information: NCT04575961 .

PD-1 blockade plus chemotherapy followed by concurrent SBRT with SIB as preoperative therapy for patients with potentially resectable pancreatic cancer: A single-arm phase 2 study.

e16312 Background: Pancreatic cancer has 10% low rate of early diagnosis and resection due to its insidious onset and poor prognosis. We aimed to assess the safety and efficacy of a new mode of preoperative therapy for patients with Potentially Resectable Pancreatic Cancer. Methods: This is a single arm clinical trial (NCT05634564). Gemcitabine (1000 mg/m2) and nabpaclitaxel (125 mg/m2; AG) were administered to patients with LAPC or BRPC on days 1 and 8, along with tislelizumab (200 mg) on day 1 intravenously (IV) every three weeks. Concurrently, the patients underwent stereotactic body radiotherapy (SBRT) with simultaneous integrated boost (SIB)during the third cycle of treatment. Surgical intervention was reassessed after four cycles of treatment. Objective response rate (ORR) was the primary endpoint and Disease control rate (DCR), R0 resection rate, median overall survival (mOS), median progression free survival (mPFS) rate, time to progression (TTP) and safety were analyzed as secondary endpoints. Results: Between May 2020 and April 2023, 62 patients with LAPC or BRPC were enrolled. Until the last follow-up time (January 30, 2024) ,56 of them included in the intention-to-treat (ITT) analysis who completed at least three cycles of tislelizumab plus AG and underwent concurrent radiotherapy. The median age in intention-to-treat analysis was 65 years. 25 patients had a best response of partial response, the ORR was 44.6%, DCR was 100%. Thirty-one patients met the criteria for surgical resection after treatment, 9 of whom refused surgery and continued conservative treatment. 22 patients underwent resection, and the R0 resection rate was 95.45%. Two of the 22 resected patients achieved pathologic complete response (pCR) and five patients achieved major pathological response (MPR). The pathologic complete response rate was 9.10% and significant pathological response rate was 31.82%. The TTP was 19.38 months (95% CI: 12.8%-27.9%), and the mOS was 21.32 months (95% CI:15.9%-NR). The 12-months PFS rate and 12-months OS rate were 59.9% (95% CI:45.2%-71.8%) and 74.4% (95% CI:59.9%-84.3%), respectively. Grade 5 adverse events were not observed. The most common grade 3-4 hematological and non-hematological toxicities were leukopenia (17.9%), neutropenia (16.1%), anemia (8.9%), thrombocytopenia (7.1%), rash: dermatitis (7.1%), Peripheral neuropathy (3.6%). Conclusions: Anti-PD-1 inhibitor tislelizumab plus AG chemotherapy followed by concurrent SBRT with SIB significantly prolonged mPFS rate, as well as R0 resection rate of surgical patients, and also improved the major pathological response rate. Clinical trial information: NCT05634564 .

Breast cancer recurrence rate after mastectomy in young females.

e12591 Background: Breast cancer is the most commonly diagnosed female cancer worldwide and the most common cause of cancer mortality in women. Surgical treatment of early breast cancer includes lumpectomy or mastectomy with or without reconstruction. Despite the surgeon’s best effort to perform a radical resection of the breast tissue during mastectomy to achieve locoregional control, residual fibroglandular tissue was found in 20% of breasts on postoperative breast MRI, which carries a risk of recurrence. Younger women with breast cancer have inferior survival rates despite receiving more aggressive therapy. Tumors in young women are more likely to be poorly differentiated, hormone receptor-negative, have a high proliferation index, and more lymphovascular invasion, which is partially explained by patients’ genetic profile. Another factor that could contribute to poor outcomes is the advanced stage at the time of diagnosis, including larger tumor size and higher rates of axillary lymph node positivity. This knowledge has motivated us to conduct this study that is dedicated to looking at the recurrence rate in young females following mastectomy. Methods: This is a retrospective study that collected data from young female patients who were diagnosed with breast cancer between January 2010 and August 2018, had an age at diagnosis of 18-45 years old, and underwent unilateral or bilateral mastectomy with or without reconstruction. The study also looked at the patient’s risk factors and genetic profile. Results: A total of 115 patients were diagnosed with early-stage breast cancer between January 2010 and August 2018 and underwent mastectomy. 81.74% were Caucasian females, and 8.7% were African American females. The mean age of diagnosis was 36.9 years. The mean BMI was 30.5 kg/m2. 59.13% of patients had a family history of breast cancer. The most common genetic mutations were BRCA1 at 7.83% and BRCA2 at 8.7%. 71% of patients underwent a bilateral mastectomy. 76% of patients had reconstruction. 77% of tumors were ER-positive, 68% PR-positive, and 26% HER2-positive. 49.4% of tumors were Nottingham grade 3. 52% of patients had no nodal involvement, while 35% had N1 disease. 34.6% had lymphovascular invasion. We found that 18/115 patients had recurrence of breast cancer following mastectomy. 5/17 patients had locoregional recurrence, while 12/17 patients had a distant recurrence; 1 patient’s recurrence data was unavailable. The median time to recurrence was 1147.5 days (335 to 3107). The 5-year recurrence free survival rate is 86% ± 3%. Conclusions: Our study found that 15.65% of young females had recurrence after mastectomy. To our knowledge, this is the first dedicated study to look at the recurrence rate after mastectomy in this young, high-risk patient population. Our study aims to encourage larger studies in young females with breast cancer to help tailor the treatment plan in this population.

Short-course radiotherapy (SCRT) followed by fruquintinib plus adebrelimab and CAPOX in the total neoadjuvant therapy of locally advanced rectal cancer (LARC): A multicenter, single-arm, open-label, phase II study.

TPS3643 Background: For LARC patients (pts), long-course concurrent chemoradiotherapy or SCRT followed by chemotherapy is recommended by the NCCN guidelines (Version 1.2024) as neoadjuvant therapy. Compared with chemoradiotherapy, the addition of immune checkpoint inhibitors (ICIs) or anti-angiogenic drugs could further improve complete response (CR) rate in the neoadjuvant treatment of LARC. Fruquintinib, a highly selective small-molecule inhibitor of VEGFR-1, -2, and -3, has gained FDA approval for pts with metastatic colorectal cancer previously treated. For pts with LARC at high risk of recurrence, the CR rate of SCRT followed by chemotherapy was 29%. There is an urgent need for new therapeutical options to improve the CR rate in these pts. This study introduces an innovative approach, combining SCRT, chemotherapy, Fruquintinib, and ICIs as a total neoadjuvant therapy for high-risk LARC pts. Methods: This is a multicenter, single-arm, open-label, phase II study (NCT06234007) investigating the efficacy and safety of SCRT sequential fruquintinib, combined with adebrelimab (an anti-PD-L1 monoclonal antibody) and CAPOX in pts with LARC. Eligible participants were 18 years or older, with an ECOG PS of 0–1, and a biopsy-proven, newly diagnosed, primary, LARC, classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for surgery. Total neoadjuvant therapy included SCRT (5 × 5 Gy over 5 days, 1-week rest) followed by six cycles of fruquintinib (4mg, qd, po, q3w. For the initial 6 pts in the safety run-in period, dosage was adjusted based on dose-limited toxicities in the 1st cycle) combined with adebrelimab (1200mg, iv, d1, q3w) and CAPOX (q3w). Subsequently, pts who did not reach clinical CR underwent total mesorectal excision, others received the “Watch and Wait” policy or surgery. Primary endpoint was CR rate (including clinical CR & pathologic CR). Secondary endpoints included 3-year event free survival rate, overall survival, R0 resection rate and adverse events (AEs). Exploratory endpoints aimed to evaluate the correlation between potential biomarkers and efficacy. Using PASS 15 software (version 15.0.5.0), in the Tests for One Proportion analysis, with a two-sided α of 5% and to guarantee the power over 80%. The null hypothesis of CR rate was 29%, and the alternative hypothesis was 51%, accounting for a 10% drop-out rate, resulting in a sample size of 39 pts. With the 6 pts in the safety run-in period, a total of 45 pts would be enrolled in the study. Until Feb 1, 2024, 7 of planned 45 pts have been enrolled. Clinical trial information: NCT06234007 .

Clear cell and non-clear cell renal cell carcinoma in young adults: clinicopathological features, survival outcomes and prognostic factors.

Renal cell carcinoma (RCC) is infrequent among young adults. Few studies reported the outcome of RCC in young adults by pathological subtypes. The purpose of this study was to explore the clinicopathological features, survival outcomes and prognostic factors of young adult patients with clear cell (CCRCC) and non-clear cell renal cell carcinoma (NCCRCC). This study included young adult patients aged 18-40years who were diagnosed as renal cell carcinoma (RCC) between 2012 and 2022 at Peking University Third Hospital. All patients underwent either partial nephrectomy or radical nephrectomy, and some received adjuvant therapy. A comparative analysis was performed to investigate the differences in clinicopathological characteristics between the cohort of CCRCC and NCCRCC. Kaplan-Meier survival analysis was utilized to plot survival curves for young adults with RCC. The univariate and multifactorial prognostic analyses were conducted using the log-rank test and COX proportional hazards model. A total of 300 RCC patients aged 18-40years were performed, of which 201 were diagnosed with CCRCC (67%) and 99 were diagnosed with NCCRCC(33%). The NCCRCC included 29 cases (9.7%) of chromophobe RCC, 28 cases (9.3%) of MiT family translocation RCC, 22 cases (7.3%) of papillary RCC, 11 cases (3.7%) of low malignant potential multifocal cystic RCC, and 6 cases of unclassified RCC (2.0%), 2 cases of mucinous tubule and spindle cell carcinoma (0.7%), and 1 case of FH-deficient RCC (0.3%).The mean age was 33.4±6.1years old. The overall and progression free 5-year survival rate was 99.1 and 95.3%, respectively. The NCCRCC cohort demonstrated a statistically significant decrease in progression-free survival (PFS) rate when compared to the CCRCC cohort (p<0.001). There was no statistically significant difference observed in overall survival (OS) (p=0.069). Pathological stage was a significant independent predictor for OS (p=0.045). Pathological stage and nuclear grade were both independent predictors for PFS (p=0.020; p=0.005). The clinical and pathological features of young adults diagnosed with CCRCC exhibit notable distinctions from those of NCCRCC patients. The survival outcome was significantly influenced by the pathological stage, while both the nuclear grade and pathological stage had a significant impact on tumor progression. This study offered significant contributions to the understanding of the clinicopathological characteristics and prognostic determinants of renal cell carcinoma (RCC) in young adults.

Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up

ObjectiveBrachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs.Materials and methodsThe relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis.ResultsAccording to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2–3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level.ConclusionIn general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.

Structure-specific rigid dose accumulation dosimetric analysis of ablative stereotactic MRI-guided adaptive radiation therapy in ultracentral lung lesions.

Definitive local therapy with stereotactic ablative radiation therapy (SABR) for ultracentral lung lesions is associated with a high risk of toxicity, including treatment related death. Stereotactic MR-guided adaptive radiation therapy (SMART) can overcome many of the challenges associated with SABR treatment of ultracentral lesions. We retrospectively identified 14 consecutive patients who received SMART to ultracentral lung lesions from 10/2019 to 01/2021. Patients had a median distance from the proximal bronchial tree (PBT) of 0.38 cm. Tumors were most often lung primary (64.3%) and HILUS group A (85.7%). A structure-specific rigid registration approach was used for cumulative dose analysis. Kaplan-Meier log-rank analysis was used for clinical outcome data and the Wilcoxon Signed Rank test was used for dosimetric data. Here we show that SMART dosimetric improvements in favor of delivered plans over predicted non-adapted plans for PBT, with improvements in proximal bronchial tree DMax of 5.7 Gy (p = 0.002) and gross tumor 100% prescription coverage of 7.3% (p = 0.002). The mean estimated follow-up is 17.2 months and 2-year local control and local failure free survival rates are 92.9% and 85.7%, respectively. There are no grade ≥ 3 toxicities. SMART has dosimetric advantages and excellent clinical outcomes for ultracentral lung tumors. Daily plan adaptation reliably improves target coverage while simultaneously reducing doses to the proximal airways. These results further characterize the therapeutic window improvements for SMART. Structure-specific rigid dose accumulation dosimetric analysis provides insights that elucidate the dosimetric advantages of SMART more so than per fractional analysis alone.

Which Surgical Technique for Liver Resection is Favourable in Patients with Colorectal Liver Metastases?

Abstract Background The liver is the most common metastatic site after curative treatment for colorectal cancer (CRC). Around 50% of all patients with CRC will develop colorectal liver metastases (CRLM). Liver resection (LR) represents a curative treatment option. Benefits of anatomic (ALR) versus non-anatomic liver resection (NALR) show a lack of consistent evidence. While ALR seems to be associated with a higher postoperative complication rate, NALR could lead to more recurrences. Aims We investigated complication and survival rates of patients with CRLM after both resection types. Methods This is a multicentre cohort study using retrospectively and prospectively collected data. All patients undergoing LR for CRLM between 2009 and 2020 from 3 specialised centres in Switzerland and Germany were included. Complication and survival rates after ALR versus NALR were analysed using uni- and multivariate Cox regression models. Results 624 patients were included. Median follow-up time was 25.49 months. In 292/624 patients (47%) ALR was performed, while 53% underwent NALR. Complications according to the Clavien-Dindo classification have been observed significantly more often in the ALR group (p=0.001). Especially severe complications grade III and IV have been more present after ALR (36/292 vs. 26/332 and 13/292 vs. 11/332, respectively). Both, length of ICU and postoperative hospital stay have been significantly longer in the ALR group (p&amp;lt;0.001 each). The uni- and multivariate models have shown no significant differences in overall survival (OS) and recurrence free survival rates (RFS) between both groups (for OS adjusted HR of 0.84 (95% CI 0.59 - 1.21; p=0.35) and for RFS adjusted HR 0.92 (95% CI 0.69 - 1.22, p=0.56)). Conclusion This multicentre prospective study investigating ALR versus NALR for CRLM has shown no significant differences in OS and RFS. However, postoperative complications have been reported significantly more often after ALR. NALR seems to be the better choice for patients with CRLM undergoing LR.

Clinical analysis of 18 children with aggressive mature B-cell lymphoma after liver transplantation

Objective: To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation. Methods: This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis. Results: Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and/or modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions: The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.

Clinical Outcome of Colorectal Cancer Patients with Concomitant Hypertension: A Systematic Review and Meta-Analysis.

Arterial hypertension is regarded as a possible biomarker of treatment efficacy in colorectal cancer. Also, extended anti-angiogenic use in the metastatic treatment of the colorectal neoplasm may result in elevated blood pressure. We carried out a systematic review and meta-analysis to assess the clinical outcome of colorectal cancer patients with concomitant hypertension (HTN). We conducted a systematic search on Embase, Web of Science, Scopus, PubMed (Medline), the Cochrane Library, and CINAHL from inception until October 2023 for articles that addressed the relationship between HTN and progressive free survival (PFS), overall survival (OS), and overall response rate (ORR) for the first and second line of systemic therapy in patients with metastatic colorectal cancer. Eligibility criteria were met by 16 articles out of 802 screened studies. Pooled analysis showed that HTN was associated with significantly improved PFS (HR: 0.507, 95% CI: 0.460-0.558, p ≤ 0.001) and OS (HR: 0.677, 95% CI: 0.592-0.774, p ≤ 0.001) in patients with metastatic colorectal cancer. In addition, the pooled RR of HTN for the ORR (RR: 1.28, 95% CI: 1.108-1.495, p = 0.001) suggests that HTN could be a predictive factor of ORR in patients with metastatic colorectal cancer. Elevated blood pressure is associated with better clinical outcomes in patients with metastatic colorectal cancer.

Prognostic Evaluation of HER2-positive Early Breast Cancers Using Clinico-pathological Criteria.

HER2-positive breast carcinomas (BCs) generally behave more aggressively and show higher cytological and histological grade than HER2-negative BCs. However, the clinical properties of HER2-positive early BCs have not been studied extensively. Hence, the therapeutic significance of neoadjuvant chemotherapy (NAC) for this BC remains debatable. We retrospectively examined the clinicopathological features of 94 HER2-positive early BCs who perioperatively received anti-HER2 drugs, without undergoing NAC prior to surgery. The patients' five year-disease free survival (DFS) and overall survival (OS) rates were 95.6% and 100%, respectively. Univariate analysis demonstrated significant differences in distant metastasis-free survival (DMFS) between clinical and pathological tumor stages (T stages). Pathological T1 stage and clinical T1 stage tumors showed significantly higher DMSF than pT2-3 and cT2-3 (p=0.0002 and 0.0294). Multivariate analysis disclosed no significant differences in DFS, OS, and DMFS with respect to preoperative clinical tumor stage, patient age, type of surgery, postoperative therapy, and pathological factors. Recurrences occurred in nine patients: four (4.3%) and five (5.3%) patients showed local and distant recurrences, respectively. One patient with cT2 BC died of disease. Interestingly, four of the five BCs with distant recurrence pathologically demonstrated lymph vessel invasion. The prognoses of patients with HER2-positive stage cT1/2N0M0 BC were highly favorable. The indications for NAC in small, localized, and node-negative HER2-positive BC should be carefully assessed based on the presence of a larger tumor size, postoperative pathological evaluation of tumor size, and lymph vessel invasion.

Does depressurization of the portal vein before liver transplantation affect the recurrence of HCC? A nested case-control study

BackgroundPortal hypertension (PHT) has been proven to be closely related to the development of hepatocellular carcinoma (HCC). Whether PHT before liver transplantation (LT) will affect the recurrence of HCC is not clear.Methods110 patients with depressurization of the portal vein (DPV) operations (Transjugular Intrahepatic Portosystemic Shunt—TIPS, surgical portosystemic shunt or/and splenectomy) before LT from a HCC LT cohort, matched with 330 preoperative non-DPV patients; this constituted a nested case-control study. Subgroup analysis was based on the order of DPV before or after the occurrence of HCC.ResultsThe incidence of acute kidney injury and intra-abdominal bleeding after LT in the DPV group was significantly higher than that in non-DPV group. The 5-year survival rates in the DPV and non-DPV group were 83.4% and 82.7% respectively (P = 0.930). In subgroup analysis, patients in the DPV prior to HCC subgroup may have a lower recurrence rate (4.7% vs.16.8%, P = 0.045) and a higher tumor free survival rate (88.9% vs.74.4%, P = 0.044) after LT under the up-to-date TNMI–II stage, while in TNM III stage, there was no difference for DPV prior to HCC subgroup compared with the DPV after HCC subgroup or the non-DPV group.ConclusionCompared with DPV after HCC, DPV treatment before HCC can reduce the recurrence rate of HCC after early transplantation (TNM I-II). DPV before LT can reduce the recurrence of early HCC.

Abstract PO4-20-03: HIPEx: Adjuvant palbociclib plus endocrine therapy in ER-positive HER2-negative early breast cancer with high recurrence score according to GenesWellTM BCT; a multi-center single arm phase II clinical trial (KCSG BR 19-13)

Abstract Background: In estrogen receptor (ER)-positive human epidermal growth factor receptor2 (HER2)-negative early breast cancer (EBC) patients, NCCN treatment guideline recommend 21-gene tests for decision of adjuvant chemotherapy if tumor size is over 0.5cm or node positive disease. In addition, GenesWellTM BCT is a prognostic assay that predict the risk of recurrence in patients with ER-positive HER2-negative and nodal stage 0-1 EBC. According to gene tests, EBC patients with high recurrence risk would have help from adjuvant chemotherapy to increase the rate of disease free survival but toxicities of chemotherapy are not negligible. Therefore, the effort for escaping adjuvant chemotherapy has been performed and currently CDK4/6 inhibitor would be considered as the substitute for cytotoxic chemotherapy in ER-positive HER2-negative EBC patients. Methods: HIPEx trial is a multi-center, phase II clinical trial to determine the efficacy of adjuvant palbociclib plus endocrine therapy in ER-positive HER2-negative EBC with high recurrence score according to GenesWellTM BCT (NCT04247633). Eligible patients are women who received curative surgery and diagnosed as ER-positive, HER2-negative and pathologic stage T1b-T2 and/or N0-1. Clinical recurrence risk is high according to the modified Adjuvant! Online guideline and GenesWellTM BCT score is 4 or more which being genomic high risk. Other criteria include ECOG performance status ≤1, adequate organ functions and availability of an archival surgical specimens. Patients receive palbociclib 125mg once daily for 21 days of 28-day cycle plus tamoxifen or aromatase inhibitor (anastrozole, letrozole or exemestane) once daily for every day. Palbociclib would be taken for two years and endocrine therapy for five years or more. If adjuvant radiotherapy is required, palbociclib should be taken two weeks after the end date of radiotherapy. If patients are premenopausal status, GnRH agonist is allowed. Primary endpoint is 3-year event free survival (EFS) rate of high clinical and genetic risk ER-positive EBC. Secondary endpoints include 3-year overall survival, quality of life, safety and tolerability of palbociclib with endocrine therapy as an adjuvant setting, exploratory analysis of predictive and prognostic biomarkers and the performance of GenesWellTM BCT for 3-year EFS rate. In total, 578 patients would be enrolled in this trial. Based on the previous results of GenesWell™ BCT in Korea, the 3-year EFS rate for the past control group (chemotherapy followed by endocrine therapy) is 87.0% and the treatment group in this clinical trial is assumed to be 90.5%.(hazard ratio for EFS = 0.717). Null hypothesis is the 3year-EFS rate in patients received adjuvant palbociclib and endocrine therapy is not less than that of the past control group. Alternative hypothesis is the 3year-EFS rate of this trial is less than that of the past control group (one-sided). Significance level is 0.025, power is 0.80. Considering 10% drop out rate, 4-years of accrual patient enrollment and 3-years of follow up period, 578 patients were required in this clinical trial. Citation Format: Ji-Yeon Kim, Sung Hoon Sim, Jieun Lee, In Hae Park, Kyong Hwa Park, Seock-Ah Im, Jee Hung Kim, Kyoung Eun Lee, Jeong Eon Lee, Jai Min Ryu, Young Kee Shin, Yeon Hee Park. HIPEx: Adjuvant palbociclib plus endocrine therapy in ER-positive HER2-negative early breast cancer with high recurrence score according to GenesWellTM BCT; a multi-center single arm phase II clinical trial (KCSG BR 19-13) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-03.

Abstract PO3-04-04: Long term survival of metastatic HER2 positive breast cancer patients with no radiographic evidence of disease (NED) on HER2 antibody therapy

Abstract Introduction A small proportion of women with human epidermal growth receptor 2 (HER2) positive metastatic breast cancer (mBC) achieve “no evidence of disease” (NED) status with HER2 monoclonal antibody therapy. Patients who achieve NED status have excellent long term outcomes with overall (OS) and progression free survival (PFS) rates greater than 95%. Presently there are no reliable biologic or clinical factors which are predictive of NED. It is also unclear in NED patients when it would be safe to discontinue therapy. Therefore, even in HER2+ mBC NED patients, HER2 therapy is often continued indefinitely. In this study, we characterize clinical outcomes in HER2+ mBC patients who achieved NED status and received HER2 antibody therapy for 5+ years. Methods We conducted a retrospective analysis of patients at a U.S. academic medical center. Patients with HER2+ mBC who had received at least 5 years of either trastuzumab or trastuzumab/pertuzumab (from 2014- 2023) were identified for our NED cohort. For a non-NED comparator group, we identified women with stage IV HER2+ mBC from the tumor registry (from 2012-2021). Descriptive statistics were used to describe the demographic information and clinical characteristics. Kaplan-Meier method with log-rank test was used to analyze OS and PFS between both patient cohorts. Results 102 patients were identified that received trastuzumab or trastuzumab/pertuzumab for 5+ years. From this group, 33 patients were identified as NED based on clinical documentation and imaging. From our tumor registry data, there were 58 stage IV HER2+ patients. 34 patients met inclusion criteria for our non-NED cohort. The median follow-up time was 132 (range: 39 - 296) months for the NED cohort and 26 (range: 1-99) months for the non-NED cohort. The average diagnosis age was significantly older for the NED cohort (61 vs. 52 years, P=0.001). No other significant differences with respect to hormone receptor expression, race, or the presence of brain metastases were observed between groups. With respect to HER2 therapy, 61% of NED patients had received trastuzumab alone, and 39% trastuzumab/pertuzumab. By contrast in the non-NED cohort most received trastuzumab/pertuzumab (59%). The median time on HER2 therapy for the NED group was 125 months—70% of patients in the NED cohort were still receiving therapy vs, 12% for the non-NED cohort. As expected, the median OS (NR vs. 25.5 months; P&amp;lt; 0.0001) and PFS (NR vs. 7.9 months; P&amp;lt; 0.0001) were significantly longer in the NED cohort. 5 and 10 year OS rates for the NED cohort were 90.5% (95% confidence interval (CI): 80.8-100%) and 87% (95% CI: 75.9-99.8%), respectively. By contrast, for the non-NED cohort 5 and 10 year OS rates were only 21.3% (95% CI: 11.06-41.1%) and 0% (95% CI: 0-0%), respectively. 5 and 10 year PFS rates were 84.1% (95% CI: 72.2-97.9%) and 76.6% (95% CI: 67.7-93.6%), respectively for the NED cohort, and both were 0% for the non-NED cohort. The presence of brain metastases in the NED cohort was associated with reduced 5 and 10 year OS rates: 60% (95% CI: 29.3-100%) and 40% (95% CI: 13.7-100%), respectively. We observed in the NED cohort was associated with a drop in ejection fraction and clinically significant heart failure in 24% of patients while on HER2 therapy. Conclusions HER2+ mBC patients who achieve NED status have an excellent prognosis with starkly different clinical outcomes compared to HER2+ mBC patients who do not. We observed that 10 year OS rates in HER2+ NED patients was approximately 90%, which did not differ from 5 year OS rates. This suggests that HER2 therapy could be potentially discontinued after 5 years in mBC patients who achieve NED. More studies are needed to develop robust predictive markers for patients likely to achieve NED with HER2 targeted therapy. Citation Format: Alexis Bennett, Zhengyi Chen, James Martin, Naji Mallat, Pingfu Fu, Alberto Montero. Long term survival of metastatic HER2 positive breast cancer patients with no radiographic evidence of disease (NED) on HER2 antibody therapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-04-04.

Abstract PO5-20-04: A Phase II Study of Ribociclib and Endocrine Treatment of Physician’s Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer (RaPhLRR Study)

Abstract Background Hormone receptor positive (HR+) breast cancer (BC) is the most common subtype of BC (70-80%). This subset tends to have good prognosis, therefore most patients with localized disease have excellent long-term survival, approaching 100% 5-year relative survival. However, 10% of patients experience loco-regional recurrence (LRR) within 5 year of final surgical management of the primary disease-well within the typical treatment window of adjuvant endocrine therapy. Few studies exists to guide the systemic treatment of patients who have suffered LRR of HR+ HER2 - BC. The randomized controlled CALOR trial demonstrated no benefit to systemic cytotoxic chemotherapy for this subgroup of patients and persistent high rate of subsequent recurrences (50% within 10 years on LRR event). There is no standard of care for managing this patient population. The combination of ribociclib and endocrine therapy (ET) (fulvestrant and aromatase inhibitors) is FDA approved for management of unresectable recurrences and metastatic HR+HER- BC (MONALEESA trials). CDK4/6 inhibitors have been investigated in early BC setting too, several trials showing positive results (monarchE, NATALEE). Data is needed to investigate their use in patients with LRR. Trial design This is a multicenter, single arm phase II study to evaluate efficacy and safety of ribociclib and ET in patients with LRR of HR+HER2- BC. Treatment includes ribociclib for 36 months, 600 mg daily for 21 days, 28-day cycle plus physician’s choice ET for 60 months (fulvestrant or AIs). Ribociclib dose was chosen based on approved dose in metastatic BC. Eligibility Criteria Patients ≥ 18 of age, with LRR of BC (ipsilateral breast, axilla, regional lymph nodes, chest wall), histologically confirmed estrogen receptor positive and/or progesterone receptor positive, HER 2 negative. Patients must have adequate local treatment for LRR (surgery and/or radiation) with negative microscopic margins, no evidence of distant metastatic disease. Prior treatment with neo-adjuvant and adjuvant chemotherapy and ET is allowed, no prior CDK 4/6 inhibitor in the last 12 months. Pre and post-menopausal women are allowed. Patient must enroll within 6 months of the last local therapy. Specific aims Primary objective: to estimate subsequent recurrence-free survival (RFS) at 3 years for ribociclib when administered with ET in patients with HR + HER2- BC with adequately resected local recurrence. Secondary objectives: to estimate distant metastasis-free survival and overall survival, to evaluate safety and tolerability, to identify predictors of LRR. Correlative analysis will explore prognostic and predictive biomarkers of treatment with ribociclib and ET and potential molecular mechanisms of resistance to treatment. Statistical Methods From previous published data (J Clin Oncol. 2018 Apr 10;36(11):1073-1079), we assume that patients receiving standard of-care management following recurrence would have a recurrence free survival (RFS) rate of 80% at 3 years and that treatment with ribociclib + ET will increase it by 7%. We wish to have at least 80% power at that significance level of 0.0487 to correctly detect that improvement in RFS rate at 3 years from 80 to 87%. Because only an improvement in RFS rate is of clinical interest, we have a directional hypothesis, and have used a 1-sided alpha. Using a one-sample survival study design, with assumed accrual duration of 3-years and additional follow-up time of 3 years, the minimum sample size requirement is N=180 patients. Target accrual The minimum sample size requirement is N=180 patients. A bigger sample size of N=200 patients will achieve a power of at least 84%. Current accrual is 6/200. This study will be open at up to 35 sites. Contact information The study is being administered through the HCRN, it can be identified as BRE20-468, NCT05467891, ocdanciu@uic.edu Citation Format: Oana Danciu, Nancy Chan, Kari Wisinski, Trish Millard, Kathleen Kemmer, Sneha Phadke, Zhengjia Chen, Ana Cuesta Fernandez, Melanie Clark, Alison Conlin, Coral Omene, Sima Ehsani, Stephanie Dublis, Vijayakrishna K. Gadi. A Phase II Study of Ribociclib and Endocrine Treatment of Physician’s Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer (RaPhLRR Study) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-04.

The impact of purified protein derivative prior to intravesical bacillus Calmette-Guérin for the treatment of patients with non-muscle invasive bladder cancer.

The aim of this study is to investigate the impact of the intradermal injection of purified protein derivative (PPD) and PPD skin test reactions on the oncological outcomes of patients with non-muscle invasive bladder cancer (NMIBC) treated by trans-urethral resection of bladder tumor (TURBT) and adjuvant intravesical BCG. The study included 100 consecutive patients with NMIBC prospectively given intradermal PPD 1-2 weeks before starting BCG therapy. Another 100 patients with NMIBC not given intradermal PPD before starting BCG were chosen as a historical control. The control group was chosen to be matching with the study group regarding baseline characteristics. The study group was divided into 2 subgroups with positive and negative reaction to PPD skin test. Oncological outcomes, immunological markers (TNF-α and IL-6) changes and BCG side effects were evaluated. There were no significant differences between patients who received PPD or not regarding the 2-year recurrence free survival (RFS) rates and progression-free survival (PFS) rates and immunological markers changes. The 2-year RFS and PFS rates were significantly higher in patients with positive reactions. Post-induction values of immunological markers increased in all patients with a significant increase in patients with positive reactions. BCG side effects were significantly higher in patients with positive reactions. The intradermal injection of PPD before intravesical BCG has no impact on oncological outcomes of patients with NMIBC treated with TURBT and intravesical BCG. However, the PPD skin test reactions before BCG therapy can predict the oncological outcomes, BCG side effects and the immunological outcomes of patients.

Microsurgical reconstruction for head and neck in patients with end-stage renal disease undergoing dialysis.

Free flap transfer for head and neck defects has gained worldwide acceptance. Because flap failure is a devastating outcome, studies have attempted to identify risk factors-including renal failure. We sought to determine whether end-stage renal disease (ESRD) patients undergoing dialysis are at increased risk of flap failure following microsurgical head and neck reconstruction. The study's participants were patients who underwent free flap reconstruction in the head and neck region at Hualien Tzu Chi Hospital between January 2010 and December 2019. We used the National Health Insurance "Specific Diagnosis and Treatment Code" to identify patients undergoing dialysis; these patients comprised the dialysis group, whose members were matched to a non-dialysis group for age and gender. The dependent variables were flap survival rate, take-back rate, and flap failure risk between the dialysis and non-dialysis groups. We included 154 patients in the dialysis (n = 14) and non-dialysis (n = 140) groups. The groups were similar in terms of age and most comorbidities, except diabetes mellitus, hypertension, and coronary artery disease, which were more prevalent in the dialysis group. The dialysis and non-dialysis groups had similar flap survival rates (100% vs. 92.9%; p = .600). Twenty-three patients underwent take-back surgery, most in the non-dialysis group (14.3% vs. 15.0%; p = 1.000). Patients in the dialysis group were more likely to have prolonged intensive care unit stays; however, dialysis alone did not predict flap failure (OR: 0.83; p = .864). This study found no significant differences in free flap survival and take-back rates between patients with and without dialysis. Dialysis did not increase the risk of flap failure following microsurgical head and neck reconstruction in this study; however, prospective, randomized controlled trials are needed.