bluuebunny/crossref_metadata_2025 huggingface dataset:
OP-TNT: Phase II study of total neoadjuvant chemoradiotherapy followed by local resection for early distal rectal carcinoma.
Authors: Xian Zhang , Qian Yang , Wei Ye , Ren Li , Ye Lechi , Zhong Yunshi , Chang Wenju , Feng Qingyang , Rao Shengxiang , Liu Liheng , Huang Lihong , Ji Yuan , Wang Yichen , Xu Jianmin , Wang Jian
Published: January 2025

177

Background:
Surgery is standard of care for pMMR early distal rectal cancer (RC), which can be partially exempted by totally neoadjuvant chemoradiotherapy (TNT) followed by watch and wait. But long-term data showed that 1/3 patients had local growth( mostly in the rectal wall)in two years. This study investigates the efficacy and safety of TNT followed by local excision( LE) for early distal rectal carcinoma (cT1-3N0M0) in order to preserve organs.
Methods:
In this single-arm, phase 2 prospective trial, patients were eligible if they were aged 18 years or older, with a performance status of 0-1,newly diagnosed, biopsy proven pMMR/MSS RC which located ≤5cm from the anal verge and staged as cT1-3N0M0. Patients were assigned to receive TNT: 6 courses of CapOx(capecitabine 1000 g/m2 PO BID D1-14, oxaliplatin 130 mg/m2 IV QD D1,Q3W), combined with concurrent long-course radiotherapy (LCRT)(45 Gy/25 Fx to the pelvis with an SIB of 50 Gy/25 Fx to the tumor bed). Evaluation was performed 12 weeks after completion of LCRT. Patients who achieved a clinical complete response (cCR) or near clinical complete response (ncCR)were assigned to LE, whereas those with >ypT1, positive margin, or neurovascular invasion after LE were recommended for total mesorectal excision (TME). The primary endpoint is the 3-year organ-preserving rate. Secondary endpoints include the pathological complete response (pCR)(encompassing response after LE and TME), adverse effects rate, 3y-disease-free survival (DFS)and 3y-overall survival (OS)rate.
Results:
From October 2022 to August 2024, 52 patients had completed therapy. Median age at evaluation and follow-up duration were 58.3 years and 11 months. Of the patients 78.8% (41/52) were defined as MRI stage T3, and 76.9%(40/52) located ≤3cm from the anal verge. Of 52 evaluable patients ,82.7% (43/52) achieved cCR/ncCR and had LE (6 via endoscopic resection and 37 through trans-anal minimally invasive surgery). Among these patients, 25.6% (11/43) were found to have residual tumors after LE, of which 6 were radical-operated while 5 refused this intervention. Nine patients who did not achieve cCR or ncCR received TME resection, and 6 of them were confirmed as pCR. The total pCR rate was 73.1% (38/52). Of all patients, 3 underwent abdominoperineal resection, and sphincter-preserving rate was 94.2%(49/52). No grade 3 or 4 adverse events were reported, and there were no treatment-related deaths. The main adverse event after local resection was the 1-3 months anterior resection syndrome.
Conclusions:
The results of interim analysis showed that tumor residue was found in patients with cCR/ncCR after TNT, similar to the regrowth rate previously reported. LE strategy may become prevention. Long-term outcomes are being followed up.
Clinical trial information: NCT05563922
.
TAS102 in combination with oxaliplatin (TASOX) for refractory metastatic colorectal cancer.
Authors: Li Sharon , Ling Fan , Misdary Christian , Liu Hao , DiRubbo Manda , Boland Patrick M , Berim Lyudmyla Derby , Gulhati Pat , Cohen Seth D. , Taff Jessica Leland , Shah Ankit , Lee Patrick , Radovich Delia , Leitner Stuart P. , Scoppetuolo Michael , Hochster Howard S.
Published: January 2025

189

Background:
TAS102 (trifluridine/tipiracil hydrochloride) is approved for use alone or with bevacizumab in late line metastatic colorectal cancer (mCRC), with overall survival benefit in phase 3 trials (RECOURSE and SUNLIGHT). Oxaliplatin is frequently reintroduced after progression, resolution of limiting neuropathy, or disease recurrence post adjuvant therapy. In preclinical studies, oxaliplatin combined with TAS102 has shown synergism. We hypothesized TASOX may be an option for patients who have progressed/recurred after FOLFOX.
Methods:
We assessed safety and efficacy of TAS102 with oxaliplatin, enrolling patients with metastatic CRC progressed on ≥2 lines of therapy including 5FU, oxaliplatin and irinotecan. Patients with recurrence during or within 6 months of adjuvant chemotherapy were allowed. Exclusion: Prior TAS102 exposure, functional impairing peripheral neuropathy, ≥Grade 3 hypersensitivity to oxaliplatin, or uncontrollable grade 1-2 hypersensitivity to oxaliplatin. Treatment continued until disease progression or unacceptable toxicity. Patients received oxaliplatin 85 mg/m2 and TAS-102 35 mg/m2 bid days 1-5 every two weeks, and bevacizumab per MD choice. The primary endpoint was overall response rate (ORR) by RECIST (by independent radiologists). Secondary endpoints included disease control rate (DCR), safety and tolerability.
Results:
54 patients enrolled; 53 received treatment on study and 48 had ≥1 disease assessment (median age 59, 58 % male, tumor RAS mutated 69%). Median time on study was 4 months (8 cycles; range 1-37 cycles). ORR was 6% (n=3), with average change in target lesions -45% (range -35 to -67%). 71% (n=34) had SD defined on study, with average change in target lesions -3% (range -29% to +20%). In those treated with bevacizumab (59%; n=28 ), 79% (n=22) had disease control vs. 75% (n=15). The most common reason for study discontinuation was progressive disease (23%, n=11). 68% (n=36) had a treatment-related adverse event (TRAE) ≥Grade 3 at any point during therapy. The most common G3 TRAEs were anemia 19% (n=10) and leukopenia 28% (n=15) at any time. Two (4%) developed grade 3 neuropathy.
Conclusions:
TASOX is effective as a 3rd line therapy for patients with mCRC. In our study, overall disease control rate was 77% with up to 19 months on study. Anemia and leukopenia are common but manageable. Bevacizumab did not seem to have as great an effect in our trial as observed in SUNLIGHT. Future studies would warrant TASOX in combination to bevacizumab in randomized trials in candidates for oxaliplatin retreatment.
Clinical trial information: NCT02848079
.
Spatial transcriptomics and lethality-associated stromal remodeling of colorectal cancer.
Authors: Wood Colin , Da Silva Filho Joao , Zhang Tengyu , Roxburgh Campbell SD , Horgan Paul G. , Edwards Joanne , Marti Matthias , Steele Colin William , Jamieson Nigel Balfour
Published: January 2025

227

Background:
Colorectal cancer (CRC) is surgically resectable and eminently screenable yet remains a lethal entity with high affinity to metastasise synchronously and metachronously. It has been proposed that cellular and extracellular components of the microenvironment contribute to metastatic potential. Dissociative profiling techniques such as bulk transcriptomic and single-cell RNA sequencing have contributed insight but limited therapeutic progress. Spatial transcriptomic (ST) assessment allows molecular profiling of tissue while preserving tissue architecture. Here we employ ST approaches to interrogate tumor compartments of primary resectable and matched synchronous CRC demonstrating stromal signatures with distinct collagen expression associated with outcome.
Methods:
25 patients with primary resectable CRC and 4 patients with matched primary CRC and liver metastasis (CRLM) underwent single-cell spatial transcriptomics using the Nanostring CosMx Spatial Molecular Imager (SMI, 1000plex gene panel) (Discovery cohort). 71681 epithelial and 88806 stromal cells with intact spatial resolution were analysed. The spatial single-cell signatures were reconstituted in 89 patients using the Nanostring GeoMx Digital Spatial Profiler (Validation cohort). 3 GeoMx compartments were analysed: Epithelial (PanCK+); Stroma (aSMA+); Immune (PanCK-aSMA-).
Results:
CosMx demonstrated 2 distinct collagen signatures: COL1A1,COL1A2,COL3A1 associated with normal fibroblasts; COL9A2 associated with cancer-related stroma and lethal subtypes of epithelial cell. In the GeoMx validation cohort, 42 patients expressed the COL1A1 signature in the aSMA compartment and 47 did not (5 year recurrence free survival: 0.88 vs 0.49, p < 0.005) with different morphological patterns of each distinct aSMA group. In patients with favourable prognosis, chemokine high epithelial subtypes expressed CXCL5 and recruited COL9A2-, IL6+ neutrophils to the surrounding microenvironment. In contrast, epithelial cells in patients with poor prognosis expressed CXCL8 and recruited COL9A2+ neutrophils which were frequently in contact with SPP1+ macrophages.
Conclusions:
We have used ST approaches to interrogate cellular compartments of CRC demonstrating stromal subtypes that impact outcome. These insights could be used in the clinical setting to quantify COL9A2 expression in aSMA+ cells to prognosticate patients. Targeting of tumor collagen has been proposed to augment existing anti-cancer therapies and this work has demonstrated COL9A2 as a potential target in need of further investigation.
Landscape of
MET
genomic alterations in colorectal cancer (CRC).
Authors: Yasin Faiza , Pavlick Dean , Ross Jeffrey S. , Cecchini Michael
Published: January 2025

247

Background:
MET signaling is implicated in the tumorigenesis of many solid tumors, including CRC. MET-targeted therapies are approved in non-small cell lung cancer with novel agents in clinical trials for tumors with
MET
exon 14 splice site mutations,
MET
amplifications, and recently MET expression. There is emerging therapeutic interest in targeting MET in CRC.
Methods:
Tumor samples from 50,500 cases of clinically advanced CRC were analyzed by hybrid capture-based comprehensive genomic profiling (CGP) that evaluated all classes of genomic alterations (GA). MSI-high status, tumor mutational burden (TMB), genomic ancestry, trinucleotide mutational signatures, and homologous recombination deficiency signature (HRDsig) were assessed for patients with activating
MET
GA. PD-L1 expression was determined by IHC (Dako 22C3 with TPS scoring system). Results were compared using the Fisher exact test with the Benjamini-Hochberg adjustment.
Results:
A total of 502 (1.0%) cases of activating GA of
MET
(METmut) were identified, including 418 cases (0.83%) with
MET
amplification (METamp), 10 (<0.1%) rearrangements, and 78 (0.1%) short variant (SV) mutations with 19 (<0.1%) cases of
MET
exon 14 splice site mutations. When compared with
MET
wild-type (METwt) CRC, the METmut CRC were of similar age (median 62 years), and numerically more likely to be male (61.4% vs 56.0%; P=.05). There were no differences in genomic ancestry (72% European ancestry for both groups). The METmut CRC featured more cases with a POLE signature (3.6% vs 0.4%; P=<0.0001) and more GA per tumor (7 vs 5; P<0.0001). MSI-high status was similar in both groups, with 4.2% in METmut and 6.0% in METwt (P=0.28). TMB levels were numerically higher in the METmut cases (TMB ≥ 10 mutations/Mb at 12.2% vs 9.0%; P=0.058). Low level PD-L1 expression (1-49% TPS) was similar in both groups (13.9% in METmut vs 13.3% in METwt), and while not statistically significant, high level PD-L1 expression (>50% TPS) was higher in the METmut group (4.3% vs 1.6%; P=0.056). The frequencies of HRDsig+ CRC were rare and similar in both groups with 1.5% in METmut and 1.7% in METwt. METmut CRC had lower frequencies of GA in
KRAS
(34.7% vs 48.8%; P<0.0001),
NRAS
(1.8% vs 4.2%; P=0.011),
APC
(72.5% vs 78.2%; P=0.009) and
PIK3CA
(12.2% vs 18.9%; P=0.0004), and higher frequencies of GA in
CDK6
(10.2% vs 0.6%; P<0.0001),
EGFR
(5.2% vs 0.2%; P=0.0002),
ERBB2
(9.6% vs 5.2%; P=0.0004),
HGF
(8.0% vs 0.8%; P<0.0001),
POLE
(4.2% vs 0.5%; P=0.005) and
TP53
(84.1% vs 75.9%; P<0.0001). In METmut CRC, ERBB2 alterations were 4.1% amplifications, 2.9% sequence mutations, 0.9% with more than one mutation.
BRAF
V600E was seen in 5.9% in METmut CRC and 8.4% of METwt.
Conclusions:
CGP reveals significant differences in the genomic landscapes of METmut CRC and METwt CRC, which may guide selection of potential rational drug combinations with novel MET-targeted therapies.
KRAS status in lung oligometastases treated with SBRT.
Authors: Loi Mauro , Valzano Marianna , Aquilano Michele , Morelli Ilaria , Frosini Giulio , Simontacchi Gabriele , Bonomo Pierluigi , Galardi Alessandra , Salvestrini Viola , Becherini Carlotta , Livi Lorenzo
Published: January 2025

264

Background:
Stereotactic Body Radiotherapy (SBRT) to lung metastases (LM) from colorectal cancer (CRC) has been applied to improve disease control in in the oligometastatic (OM) and oligoprogressive (OP) setting. The aim of this study is to assess the impact of KRAS mutational (KRASmut) status in the response to SBRT in LM.
Methods:
Data from a consecutive cohort of OM/OP CRC patients treated at our Institution with SBRT for LM from May 2019 to March 2024 were retrospectively reviewed. Patients (age, KRASmut in primary tumor, OM/OP disease, chemotherapy lines prior to SBRT) and treatment-related variables (dose regimen and Biologically Effective Dose: BED, toxicity) were collected. Local Control (LC) was defined as time from SBRT to local failure or last radiologic follow-up.
Results:
Sixty-two patients (median age: 74 years, range 49-85), accounting for 103 LM were included. LM were treated in the OM and OP setting in 65(63%) and 38(37%) cases, respectively. SBRT was delivered before chemotherapy (n=49,48%) or following first (n=31,30%) or further chemotherapy lines (n=23,22%). KRASmut was present ab initio in 49% of cases (n=50). Dose regimens included 48-60 Gy in 3-8 fractions, resulting in a median BED of 115.5 (range 76.8-151.2) Gy
10
: a BED>100Gy
10
was delivered in 92% (n=95) of treatment courses. Median follow-up was 16 (range 2-45) months. Median LC was not reached; 1- and 3 years LC rates were 85% and 67% respectively. At multivariate analysis (MVA), only a BED≤100Gy
10
(p=0.029, HR 2.99, IC95% 1.1- 9.5) and prior second or further chemotherapy line (p=0.031, HR 3.2, IC95% 1.1- 8.1) were independently correlated with impaired LC. No grade >2 toxicity was observed. Focusing on patients receiving no chemotherapy or first-line treatment before SBRT, 1- and 3 years LC rates were 92% and 77% respectively (median: NR). At MVA, while BED≤100Gy
10
(p=0.036, HR 6.96, IC95% 1.9-25.7) was associated with poorer LC, lack of KRASmut (p=0.037, HR 0.26, IC95% 0.07- 0.9) was independently correlated with improved LC.
Conclusions:
SBRT in LM from OM/OP CRC results in high LC rates, particularly with intensive regimens in non-heavily pretreated patients. No impact of KRASmut was observed. Due to possible occurrence of secondary mutations in the pretreated population, a subset analysis in the chemotherapy-naive/first-line subset suggests an impact of KRASmut in radioresistance that should be further explored in a dose-escalation perspective. Re-biopsy or liquid biopsy may be useful to identify de-novo mutations.
Outcomes of patients with peritoneal-limited metastatic gastric cancer (PLGC) undergoing bidirectional (BD) chemotherapy cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC).
Authors: Wong Evelyn Yi Ting , Liong Shun Zi , Chia Claramae , Ong Johnny Chin-Ann , Ong Hock Soo , Chan Weng Hoong , Lim Chin Hong , Lim Eugene Kee Wee , Tan Jeremy Tian Hui , Chua Glenn , Ng Kennedy Yao Yi , Lim Chiew Woon , Lam Justina Yick Ching , Chew Lee Lian , Ng Matthew C.H.
Published: January 2025

328

Background:
The prognosis of PLGC patients (pts) is poor with standard systemic therapy. PLGC pts who undergo CRS after BD chemotherapy (chemo) demonstrate prolonged survival. We retrospectively analysed the outcomes of pts who underwent BD chemo followed by CRS and HIPEC in a single institution, stratifying by peritoneal carcinomatosis index (PCI) and chemo regimen.
Methods:
PLGC pts who received BD chemo between January 2016 to September 2023 were enrolled and consented for data collection. BD chemo was either 3 weekly paclitaxel (PTX) (50mg/m2), S-1 (80mg/m2) and IP PTX (20mg/m2) or capecitabine (2g/m2), oxaliplatin (100mg/m2) (CAPOX) and IP PTX (40mg/m2). HIPEC utilised cisplatin 50mg/m2 at 40 for 60 minutes. Trastuzumab and nivolumab were given selectively. Pts without radiological progression after 24 weeks of BD chemo, with PCI7 and potential for complete resection underwent CRS including D2 gastrectomy and HIPEC. Post-resection, BD chemo was stopped. Survival was analysed by Kaplan Meier curves, adverse events (AEs) by CTCAE v5.0 and response by independent radiological review.
Results:
34 pts were enrolled with median follow-up of 26.9 months (m). Median (range) age was 51 (17 – 79) and median PCI 12 (0-29). 52.9% were female, 8.8% had Cy1 only disease and 38% had prior gastrectomy. 3 out of 6 pts with evaluable disease had partial response. Median progression-free survival and overall survival (mOS) was 9.1m and 16.5m respectively. 7 pts (20.6%) underwent CRS with median (range) PCI of 1 (0-15.0). mOS in CRS vs non-CRS pts was 23.8m vs 14.6m (p=0.4); PCI <7 vs PCI ≥7 was 23.8m vs 14.6m (p=0.63); and CAPOX vs S1/PTX systemic chemotherapy was 23.9m vs 14.6m (p=0.29) respectively. Peritoneal cytology negativity increased from 25.8% to 86.4% after BD chemo. Peritoneal lesions biopsied post-BD chemo showed no tumour cells in 64% of cases. There was no treatment-related mortality. 1 pt had IP port removal due to complications. The commonest grade 3 AE was neutropenia (14.7%). Biomarker analysis is currently being performed.
Conclusions:
BD chemo CRS HIPEC was well tolerated with longer survival in patients undergoing CRS. Evaluation of tumour using PCI post-BD chemo may be sub-optimal.
Disparities in incidence and mortality of colorectal cancer in Appalachian Kentucky.
Authors: O'Shaughnessy Lindsay Austin , Sabharwal Kennedy , Singh Chevy , Garcia Oscar , Miller Robert Clell
Published: January 2025

33

Background:
Since the late 1990s, both the incidence and mortality of invasive colorectal cancer (CRC) have decreased across the United States, including in Kentucky. Despite this, CRC incidence and mortality are above national average in Kentucky. Over the last two decades, a disparity in CRC incidence and mortality has emerged between Appalachian Kentucky (AK), a distinct eastern region, and Non-Appalachian Kentucky (NAK). This disparity is attributed to differences in social and structural determinants of health (SSDH) between these populations.
Methods:
Age-adjusted CRC incidence and mortality rates (2016-2020) for both Kentucky and the U.S. were obtained from the National Cancer Institute’s public database. Data from the Kentucky Cancer Registry were used to compare CRC incidence and mortality rates in AK and NAK counties from 1994-2021. Incidence rate ratio analyses across discrete time periods demonstrated statistical differences between these regions.
Results:
Compared to national data (2016-2020), Kentucky's CRC age-adjusted incidence and mortality rates were significantly higher: 45.9 vs. 36.5/100,000, 25.8%, for incidence, and 16.2 vs. 13.1/100,000, 23.7%, for mortality (both p<0.0001). From 1995-2003 incidence and 1994-2003 mortality of CRC, were higher in NAK, these rates eventually decreased and equalized between NAK and AK. By 2010-2015 both incidence and mortality rates were higher in AK, 55.8 vs 48/100,000, 16.3%, (p=<0.0001) and 20.1 vs 15.8/100,000, 27.2%, (p=<0.0001) respectively. The most recent data (2016-2021) shows that these significant disparities persist, with AK’s incidence and mortality 51.8 vs 44.1/100,000, 17.5% (p=<0.0001) and mortality 19.0 vs 15.1/100,000, 25.8% (p=<0.0001) higher, respectively.
Conclusions:
While CRC rates have decreased nationwide and in Kentucky, a pronounced gap in both incidence and mortality has developed between Appalachian and Non-Appalachian Kentucky. Appalachian counties—which are more rural and impoverished—face greater barriers to accessing preventive healthcare, contributing to this disparity. Additionally, AK has higher rates of obesity, poverty, smoking, and lower educational attainment and screening rates . Recent public health efforts, such as promoting stool-based screening and increasing preventive care discussions, aim to reduce these disparities. However, delays in CRC screenings during the COVID-19 pandemic— resulting in approximately 1.7 million missed colonoscopies nationally— may have skewed the most recent data, necessitating further analysis in the coming years.
Impact of race on end-of-life care among patients with esophageal cancer.
Authors: Baskar Suriya , Desai Chaula , Grewal Udhayvir Singh
Published: January 2025

337

Background:
Esophageal cancer is an aggressive malignancy with rising incidence globally. Patients with advanced esophageal cancer suffer from a heavy burden of a wide array of symptoms including dysphagia and cachexia/anorexia, necessitating the need for focused symptom management and palliative care. Studies focused on other cancer types have shown that Black patients are more likely to receive aggressive care at end-of-life (EOL) and suffer from a decline in quality of life. We sought to investigate racial differences in EOL care among patients with advanced esophageal cancer in the US.
Methods:
The National Inpatient Sample (NIS) was queried to identify all hospitalizations with esophageal cancer utilizing ICD-10 codes C15x from 2016 to 2020. Hospitalizations of White and Black patients with documented inpatient mortality events were then extracted. Demographic and clinical data were analyzed using chi squared tests, independent sample t-tests, and binary logistic regression (adjusted for age, gender, and Charlson comorbidity index or CCI). Adjusted Odds ratios (aOR) are presented with 95% Confidence intervals (CI).
Results:
A total of 15,130 patients with esophageal cancer were included, of which 13,345 (88.2%) were White and 1785 (11.8%) were Black. Hospitalizations with White patients recorded higher age, more males, and higher comorbidities per CCI. Hospitalizations with Black patients had longer lengths of stay on average, higher total hospital charges, and significantly less likely to have a Do Not Resuscitate (DNR) code status (aOR 0.81, 0.74-0.9 95% CI). Rates of inpatient palliative care consultation at EOL were significantly lower among Black patients (aOR=0.53, 0.48-0.58 95% CI). Black patients were more likely to receive aggressive intervention at EOL demonstrated by rates of blood transfusion (aOR 1.9, 1.6-2.1 95% CI), mechanical ventilation (aOR 1.7, 1.5-1.8 95% CI), and vasopressor usage (aOR 1.4, 1.2-1.6 95% CI).
Conclusions:
We present a large retrospective analysis demonstrating significant racial disparities in EOL care amongst hospitalized patients with esophageal cancer. Black patients had longer lengths of stay, lower rates of palliative care consultation and DNR code status, and higher rates of aggressive interventions at EOL. These findings may have implications for improving health care decision making for EOL care amongst minority patients with esophageal cancer.

WhiteN=13345
BlackN=1785
p-value

Age (in years)
68.24±10.67
65.12±10.36

<.001

CCI
9.4±3.3
8.6±3.9

<.001

Mean length of stay (days)
7.5±11.3
10.4±22.8

<.001

Total Cost (In thousands of dollars)
108.6±231.0
141.9±388.5

<.001

Palliative
Adjusted OR

60.9%

45.1%
.53 (.48 - .58)

<.001

DNR
Adjusted OR

63.8%

58.0%
.81 (.74 - .90)

<.001

Blood transfusion
Adjusted OR

13.0%

23.0%
1.9 (1.6-2.1)

<.001

Mechanical ventilation
Adjusted OR

31.4%

45.9%
1.7 (1.5-1.8)

<.001

Vasopressor
Adjusted OR

7.8%

10.6%
1.4 (1.2-1.6)

<.001
Prognostic analysis of pathological complete response after neoadjuvant therapy for locally advanced gastric cancer: A national, multicenter, retrospective study.
Authors: Chen Jie , Liu Yingxue , Lin Chao , Zang Lu , Xu Hao , Shang Liang , Xu Zhiyuan , Li Wei , Ma Zhiming , Zhu Chunchao , Li Ping , Yu Weihua , Yu Jiang , Zhang Jian , Cao Yi , Liu Fenglin
Published: January 2025

346

Background:
Several research findings indicate that some patients with locally advanced gastric cancer (LAGC) who undergo neoadjuvant therapy followed by curative surgery can achieve pathological complete response (pCR). Whether pCR is equivalent to cure, serves as a good prognostic indicator for long-term survival, and whether patients achieving pCR require subsequent adjuvant therapy are still unknown. Therefore, we conducted a nationwide multicenter retrospective study to investigate the long-term efficacy of patients with LAGC who achieved pCR after neoadjuvant therapy.
Methods:
Clinical and pathological data were collected from 351 patients with locally advanced gastric cancer who achieved pCR after neoadjuvant therapy between January 2018 and October 2023 at 14 medical centers in China. These patients were matched 1:1 with non-pCR patients based on age, gender, clinical T stage, and N stage. This study evaluated general clinical data, neoadjuvant treatment regimens, cycles, surgical outcomes, and follow-up information including postoperative adjuvant therapy, recurrence, metastasis, and survival status up to November 2023.
Results:
Negative Serum tumor markers, non-signet ring cell carcinoma and neoadjuvant treatment regimens were closely associated with pCR. Patients achieving pCR were more likely to reach ypN0 status after neoadjuvant therapy compared to non-pCR patients. Survival analysis showed significantly higher overall survival (OS) and disease-free survival (DFS) in pCR patients compared to matched non-pCR patients. Moreover, OS and DFS were significantly higher in ypN0 patients within the pCR group compared to non-pCR patients. However, there was no significant difference in OS and DFS between ypN+ patients in the pCR group and non-pCR patients. Additionally, postoperative adjuvant chemotherapy did not significantly impact OS and DFS in the pCR group.
Conclusions:
pCR is an independent prognostic factor for OS and DFS. However, survival benefits from pCR are limited to patients achieving ypT0N0 status, while ypT0N+ patients do not benefit from pCR. Furthermore, adjuvant chemotherapy may not improve the prognosis of patients achieving pCR after neoadjuvant therapy.
Postoperative exercise in gastric cancer patients undergoing gastrectomy: A randomized controlled trial.
Authors: Kim Hyoung-Il , Lee Tae Ho , Jeon Justin Y.
Published: January 2025

358

Background:
Faster physical recovery after gastrectomy may lead to better physical and psychological health in patients with gastric cancer. Post-surgical exercise may prevent physical dysfunction and improve recovery, but its effects on physical function are not fully explored.
Methods:
In this trial, 52 gastric cancer patients (Stage 1-3) were randomly assigned to early postoperative exercise rehabilitation or usual care (1:1 ratio). Interventions Inpatient Supervised Exercise sessions were conducted for 15 minutes once a day on Postoperative Day (POD) 1 and 2 in the ward. Home-based Exercise involved 30-minute remote exercise sessions at home once a week following discharge, with additional recommendations for daily 30-minute sessions of low to moderate-intensity aerobic exercises and bodyweight exercises. Moreover, the exercise group was provided with an exercise log and instructional videos to record the duration of bodyweight exercises and aerobic exercises. Measurements were taken three times (baseline, POD3, and the first outpatient visit 1 month after surgery). The primary outcome was a Short Physical Performance Battery (SPPB), with secondary outcomes including grip strength, 30-second sit-to-stand (STS), body composition, C-reactive protein (CRP), and quality of life (QOL).
Results:
A total of 46 (88%) participants (mean [SD] age, 60.2 [12.24] years; 26 [57%] male) completed the trial. Compliance with intervention in-patient exercise was 96% and remote exercise was 79%. The significant difference in SPPB scores of 11.4±1.3 in the exercise group compared with 10.7±1.43 usual care group (mean difference, -1.09 score; 95%CI, -1.7 to -0.4; p=<.001). Moreover, there were significant differences between groups in the STS exercise group 14.3±2.8 usual care group 13.6±4.5 (mean difference, 1.86; 95%CI, -3.3 to -0.4; p=.028), and CRP in POD3 exercise group 66.9±40.73 usual care group 103.7±54.25 (mean difference, -22.54 score; 95%CI, -46.5 to 1.4; p=.016). However, there was no significant difference in grip strength, body composition, and QOL.
Conclusions:
Postoperative exercise presents as a beneficial strategy to enhance physical recovery in patients undergoing gastrectomy, improving key physical function markers and reducing inflammation.
Clinical trial information: NCT06260293
.
PD-1 inhibitor (sintilimab) and fruquintinib plus SOX as conversion therapy for initially unresectable gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): Updated results from a single-arm, phase 2 clinical trial.
Authors: Ma Fei , Luo Suxia , Zhang Bin , Ma Qi , Ji Sheqing , Zhang Zhandong , Zhang Yonglei , Yang Wei , Peng Liangqun , Guo Dandan , Ren Jinjun , Zhang Yuan , Su Yueyue , Li Jing , Liu Wentao , Huang Jinxi , Yuan Weiwei
Published: January 2025

406

Background:
The evidence of conversion therapy for unresectable GC/GEJC is limited. Previously, preliminary results of the ongoing open-label, phase 2 study (NCT05177068) have showed promising R0 surgical conversion rate (62.1%), R0 resection rate (100%) and acceptable tolerability in unresectable GC/GEJC with sintilimab and fruquintinib plus SOX (ASCO 2024). Here we present updated results with longer follow-up duration, including more enrolled patients.
Methods:
Eligible patients were administered fruquintinib (4mg/d, po, qd, d1-14), sintilimab (200mg, iv, d1), oxaliplatin (130 mg/m
2
, iv, d1) and S-1 (40-60mg based on BSA, po, bid, d1-14) every 3 weeks for 3 or 6 cycles. One more cycle of sintilimab plus SOX was given before resection. Patients were assessed for tumor response and surgical feasibility by radiologic imaging & MDT every 3 cycles. Primary endpoint was R0 resection rate. Secondary endpoints included pathological response, ORR, PFS, OS, and safety.
Results:
As of July 30, 2024, 42 pts (37 males/5 females) with a median age of 64 years (range: 43–76), 71% ECOG PS1, 55% GEJC were enrolled. Nine (21.4%) of the 42 pts had distant metastasis and five (11.9%) pts had more than one unresectable factors. The most common unresectable factors were extensive or bulky lymph nodes 54.8% (23), liver metastasis 11.9% (5), peritoneal metastasis 4.8% (2), para-aortic lymph node metastasis 2.4% (1), and local progression 38.1% (16). Of 35 evaluable pts, ORR was 68.6% and DCR was 97.1%. Among the 29 pts who had completed surgical conversion, the R0 resection rate was 100% (29/29) and R0 surgical conversion rate was 82.9% (29/35). 10.3% (3/29) pts achieved pathological complete response (pCR), and 20.7% (6/29) pts reached tumor regression grade (TRG) 0-1. Additionally, the pathological response rate (pRR) according to JCGC (≥ Grade 1b) was 93.1% (27/29). Seven pts (16.7%) had grade 3 treatment-emergent adverse events, including 4 cases of anemia, 2 cases of neutrophil count decreased, and 1 case of each (lymphocyte count decreased, gastrointestinal hemorrhage, diarrhea, and immune-related pneumonitis). No severe surgery-related complication was observed.
Conclusions:
Fruquintinib combined with sintilimab and SOX yielded very high R0 conversion rate and R0 resection rate with a manageable safety profile in unresectable GC/GEJC, representing a potential and feasible conversion therapy regimen for this population. Survival data will continue to be followed up.
Clinical trial information: NCT05177068
.
Conversion from radical esophagectomy to definitive chemoradiotherapy after neoadjuvant chemotherapy for advanced esophageal squamous cell carcinoma: Treatment options based on chemotherapy response.
Authors: Narita Kiyoshi , Higaki Eiji , Abe Tetsuya , Fujieda Hironori , Hashimoto Shingo , Kadowaki Shigenori , Tajika Masahiro , Kodaira Takeshi , Muro Kei , Shimizu Yasuhiro
Published: January 2025

408

Background:
Radical esophagectomy after neoadjuvant chemotherapy (NAC) is the established strategy for resectable advanced esophageal cancer. However, some patients convert to definitive chemoradiotherapy (dCRT) after NAC due to reasons such as their wishes or disease progression, and their prognosis remains uncertain. We aimed to investigate the prognosis of patients who converted to dCRT.
Methods:
Patients who underwent NAC for resectable advanced esophageal squamous cell carcinoma between 2006 and 2020 were enrolled retrospectively. The prognostic impact of subsequent treatment after NAC, planned surgery or conversion to dCRT, was compared.
Results:
We analyzed 686 patients, 70 who converted to dCRT (dCRT group) and 616 who underwent surgery (Surg group). The dCRT group had a poorer prognosis than the Surg group, with more advanced tumors and poorer response to NAC. Therefore, further analysis was conducted by categorizing patients as Responders (complete or partial response) and Non-responders (stable or progressive disease) to NAC. Among Responders in the dCRT group, 76.7% achieved a complete response, and the 5-year esophageal preservation survival rate was 66.9%. The 5-year survival rates for Responders were 77.5% and 71.3% in the dCRT and Surg groups. Multivariable analysis showed that dCRT did not worsen prognosis (
P
= .706, hazard ratio = 1.13; 95% confidence interval, 0.59 to 2.16). Conversely, in Non-responders, dCRT had a significantly poorer prognosis, with 5-year survival rates of 22.3% and 45.1% in the dCRT and the Surg groups (P < .001).
Conclusions:
For patients responding to NAC, conversion to dCRT is considered a potential treatment option. The possibility of chemoselection has been suggested in the choice of treatment for esophageal squamous cell carcinoma.
Exploring the role of bispecific and CAR-T cell therapies in gastric cancer: A systematic review and meta-analysis.
Authors: Shahzad Moazzam , Basharat Ahmad , Irfan Sohaib , Noor Jawad , Mahmud Muftah , Mahmud Muftah , Mir Waleed , Mujtaba Ghulam , Khalid Muhammad Fareed , Warraich Sarmad Zaman , Jaglal Michael Vishal
Published: January 2025

465

Background:
Gastric cancer (GC) is associated with significant mortality due to the limited efficacy of current conventional treatments, necessitating the need for novel therapies. In this systematic review and meta-analysis, we aim to explore the potential role and outcomes of bi-specific antibodies and chimeric antigen receptor T-cell (CAR-T) immunotherapy in treating GC.
Methods:
Using PRISMA guidelines, searches were conducted on PubMed, Cochrane, and Clinicaltrial.gov for 'Gastric cancers', 'bispecific antibodies', and 'CAR-T therapy' as of March 30, 2024. Out of 35 studies, 9 were selected for pooled analysis in R (v4.3.3) using the Der Simonian-Laird Estimator, calculating inter-study variance and extracting data with 95% CI.
Results:
138 gastric cancer (GC) patients from 2 phase I (22.22%), 3 phase Ib (33.33%), 3 phase II (33.33%), and 1 case report (11.11%). Median age was 57 (28-77) years, and 76% (31/41) were male. Bispecific antibodies were MCLA-128 (25/138), catumaxomab (15/138), AK104 PD-1/CTLA-4 (16/138), ABL 001 DLL4VEGFA (19/138), and KN026 (25/138) while CART therapy was CT041 (38/138). The pooled overall response (OR), partial response (PR), and complete response (CR) for bispecific antibodies was 37% (95% CI, 0.12-0.71, I2=76%, n=100, p <0.01), 21% (95% CI,0.05-0.55, I2=73%, n=85, p<0.01), and 11%(95% CI, 0.02-0.38, I2=63%, n=85, p=0.03) respectively, while the pooled OR, PR, and CR for CART was 56% (95% CI, 0.40-0.71, I2=0%, n=38, p=0.41), 53%(95% CI, 0.36-0.69, I2=0%, n=38, p=0.38, ), and 12% (95% CI, 0.02-0.42, I2=38%, n=38 p=0.2), respectively. The pooled disease control rate was 75% (95%CI,0.46-0.92, I2=79%, n=80, p < 0.01) for bispecific antibodies and 27% (95% CI,0.16-0.40, I2=0%, n=65, p=0.37) had the stable disease while pooled incidence of progressive disease was 18% (95% CI,0.09-0.31, I2=0%, n=55, p=0.53). The median progressive free survival was 6.74 months, with a median overall survival of 14.75 months. Common adverse effects included anemia, diarrhea, fatigue, and cytokine release syndrome grades 1 or 2.
Conclusions:
This analysis shows promising results in GC patients using bi-specific antibodies and CAR-T cell therapy. However, further clinical trials are needed to fully explore their potential.
Use of molecular residual disease (MRD) testing with measurement of circulating tumor DNA (ctDNA) post-operatively in stage II colon cancer (SIICC) in the community-based setting.
Authors: Foster Kiran , Desai Sameer P. , Canavan Jake , Ronnen Ellen A.
Published: January 2025

53

Background:
80% of adult oncology patients (pts) are treated in the community-based setting. Data on the implementation of emerging technologies such as ctDNA testing is scant in this population. Use of adjuvant chemotherapy in SIICC pts historically was based on clinical/pathological risk factors however new data presented in mid 2022 utilizes the presence or absence of ctDNA 6-8 weeks post operatively to help risk stratify pts. The absence of ctDNA predicts a high chance of disease-free survival. Use of ctDNA was incorporated into the NCCN Colon Cancer guidelines as of 2023. In a private practice setting, we retrospectively looked at the use of ctDNA assay for adjuvant chemotherapy decision-making in SIICC pts.
Methods:
We conducted a retrospective study to quantify ctDNA testing frequency in SIICC pts in our community based oncology practice. The historical cohort was comprised of pts diagnosed prior to the NCCN guideline inclusion of ctDNA; the current cohort included pts diagnosed after the NCCN guideline change. For all pts, we reviewed clinicopathologic risk factors deemed to be high risk (positive margin, < 12 LN removed, tumor budding, lymphovascular invasion, poorly differentiated features; perforation or obstruction) and used this for stratification. Low-risk pts had no high risk features. Medical record data (office notes, pathology, molecular testing) was evaluated to determine ctDNA results including timing and use of adjuvant chemotherapy. Primary endpoint was the percent (%) of current pts who were low-risk with ctDNA testing sent compared to historical control. Secondary endpoint was the % of ctDNA testing sent within 8 weeks of curative surgery in both cohorts.
Results:
In a private practice setting, we identified low-risk SIICC pts spanning a 36-month period and categorized them into two groups: the historic cohort (A) pts were diagnosed between July 2021-Dec 2022, and the active cohort (B) pts were diagnosed between Jan 2023-July 2024. 26 pts were identified in cohort A and 36 pts were identified in cohort B to have SIICC. Out of 26 pts in cohort A, we identified 13 low risk SIICC pts; for cohort B, out of 36 pts, we identified 25 low-risk SIICC pts. The percentage of pts in each group that had ctDNA testing sent was 79.6% (10/13 pts) in cohort A and 92% (23/25 pts) in cohort B. In cohort A, 80% (8/10 pts) and in cohort B, 90.9% (20/22 pts) had ctDNA sent within 8 weeks of surgery.
Conclusions:
Incorporation of ctDNA testing in low-risk SIICC pts in a community-based setting occurred quickly. As ctDNA testing was implemented into practice, a majority of pts had the testing sent in the appropriate time frame. Future best practices, especially in the community, should incorporate tumor specific clinician oversight with use of updated pathways to ensure any recent changes to standard of care are followed.
Economic burden of hepatocellular carcinoma recurrence after curative treatment in Spain.
Authors: Varela Maria , Feliú Jaime , Garrido Margarita , Gomez-Bravo Miguel Angel , Gonzalez-Costas Sonia , Irurzun Javier , Ruiz de Alda Lucía , Vieitez Paula , Carcedo David , Crespo María , Vera Ruth , Reig Maria
Published: January 2025

640

Background:
The literature on burden of disease studies of hepatocellular carcinoma is scarce. The aim of this analysis was to quantify the economic burden of disease recurrence in very early or early-stage HCC patients who underwent liver resection, ablation or transplantation in Spain.
Methods:
A decision-tree model was developed to estimate the cost of a recurrence after curative treatment with an initial complete response of very early or early-stage primary HCC tumor over a 5-year time horizon. Clinical parameters were collected by a multidisciplinary group of experts who also validated the assumptions and results of the analysis. According to the Barcelona Clinic Liver Cancer (BCLC) recommendations, patients with recurrent HCC were classified into five HCC stages (0, A, B, C, and D) and allocated to different treatment options. A payer perspective was adopted, so only direct costs (€2024) were considered (local/locoregional treatments costs, drug acquisition and administration costs, adverse events management costs, diagnostic and follow-up costs and end-of-life costs). Sensitivity analyses were performed to assess uncertainty.
Results:
A total of 1,250 HCC recurrences were estimated in Spain, resulting in a total cost of €32,817,142 in the first year of recurrence management. After 5-years follow-up, an additional €10,1M was estimated, mainly due to patient surveillance (€2,8M) and 228 new recurrences (€5,7M). The average cost of a relapse was €26,253 euros in the first year of recurrence management, rising to €34,342 euros for 5-years follow-up. A hypothetical patient experiencing a second relapse 5 years after their first relapse would incur costs of €58,758.
Conclusions:
This study is the first in Spain to explore the economic burden of hepatocellular carcinoma. Estimating the cost of recurrence after curative treatment and complete response of a primary HCC tumor is complex and depends on multiple factors, so further studies exploring both efficacy and costs in hepatocellular carcinoma are needed.
LAPIS: Randomized phase 3 trial of chemotherapy (CTX) with and without pamrevlumab (PAM) for locally advanced pancreatic cancer (LAPC).
Authors: Picozzi Vincent J. , Khan Khurum Hayat , Hammel Pascal , Reni Michele , Lin Daniel , Lee Woo Jin , Pazo Cid Roberto A. , Sahai Vaibhav , Munoz Martin Andres J , Liu Jianjun , Zhao Ende , Carrier Ewa , Macarulla Teresa
Published: January 2025

675

Background:
PAM improved response, surgical eligibility, and resection rates when combined with CTX in phase 1/2 LAPC trials (NCT01181245; NCT02210559). LAPIS (NCT03941093) evaluated efficacy and safety of PAM + CTX in unresectable LAPC.
Methods:
LAPIS was a global, double-blind, placebo-controlled phase 3 trial of adults with treatment-naïve, -confirmed unresectable LAPC. Patients received (randomized 1:1) PAM (35 mg/kg Q2W) or placebo (PBO) plus CTX (gemcitabine + nab-paclitaxel [GnP] or FOLFIRINOX [FFX] per standard protocol) for up to six 28-day cycles. based on changes in -9, on FDG-PET, resectability, with final surgical decision made by surgeon. Primary endpoint: overall survival (OS); secondary endpoints: event-free survival (EFS), progression-free survival (PFS), and objective response rate (ORR. Safety (including treatment-emergent adverse events [TEAEs]) was evaluated in patients who received treatment.
Results:
143 and 141 patients (median [range] age, 65.0 [31–90] yrs; 53.2% male) were randomized to PAM and PBO arms. 142 and 141 received treatment: GnP, 114 (79.7%) and 112 (79.4%); FFX, 28 (19.6%) and 29 (20.6%). PAM (64.8%) and 96 PBO (68.1%) patients completed 6 treatment cycles. . Survival similar for PAM and PBO arms (Table) and did not differ by. For PAM + FFX vs PBO + FFX, respiratory, thoracic and mediastinal disorders (39.3% vs 27.6%) and skin and subcutaneous tissue disorders (53.6% vs 37.9%) occurred >10% more with PAM; TEAE frequencies were similar with PAM + GnP and PBO + GnP. One treatment-related death occurred in PAM arm.
Conclusions:
LAPIS contained important LAPC trial innovations: pre/post-CTX FDG-PET imaging, objective criteria for surgical intervention, external surgical review panel, and composite EFS measurement. Addition of PAM to CTX was not associated with additional toxicity but did not improve survival outcomes for unresectable LAPC.
Clinical trial information: NCT03941093
.

LAPIS endpoints.

PAM arm (n=143)
PBO arm (n=141)

OS, months, median (95% CI)
events=118 (82.5%)17.25 (15.47, 18.89)
events=112 (79.4%)17.94 (14.59, 20.34)
HR (95% CI)1.08 (0.83, 1.41)p=0.55

EFS,
a
months, median (95% CI)

events=99 (69.2%)5.72 (5.59, 6.01)
events=102 (72.3%)5.78 (5.62, 6.37)
HR (95% CI)1.05 (0.78, 1.39)

PFS, months, median (95% CI)
events=48 (33.6%)9.36 (7.75, 11.79)
events=44 (31.2%)9.40 (7.69, 10.84)
HR (95% CI)1.01 (0.65, 1.56)

ORR, n (%)
43 (30.1)
64 (45.4)
OR (95% CI)0.50 (0.31, 0.82)

Complete response
0
0

Partial response
43 (30.1)
64 (45.4)

CI, confidence interval; HR, hazard ratio; OR, odds ratio.

a
Earliest of 1) failure to achieve local disease-free status at end of treatment and/or after surgery; 2) local or distant recurrence/progression; or 3) death.
A systematic review of the impact of artificial intelligence in pancreatic cancer detection.
Authors: Ethakota Jahnavi , Singh Bipneet , Bai Sakshi , Kumar Danesh , Malik Devin Birsingh
Published: January 2025

685

Background:
Pancreatic cancer is the fourth leading cause of cancer deaths in the United States, and early detection remains a significant challenge. Screening the general population is not feasible, but the rise of artificial intelligence (AI) has introduced new possibilities for improving early diagnosis and patient outcomes.
Methods:
A systematic literature search was conducted using PubMed, Google Scholar, and MEDLINE using MeSH terms Artificial intelligence or AI, and diagnosis and pancreatic carcinoma or pancreatic adenocarcinoma. Prisma guidelines were adhered to, and a total of 19 studies resulted, 6 of them were retrospective studies, 4 of them were literature reviews, and 4 of them were randomized trials. The rest were duplicates. The inclusion criteria for this study is AI being used in the diagnosis, only in pancreatic cancer, within the last 5 years, only in English, and only retrospective studies were included.
Results:
One study used Digital Imaging Processing (DIP) for analyzing Endoscopic ultrasound (EUS) images from 153 pancreatic cancer patients, yielding a sensitivity of 97.98% and a specificity of 94.32%. Two studies explored Computer Aided Diagnosis (CAD) models applied to PET/CT and EUS images, achieving a sensitivity of 95.23% and specificity of 97.51% in PET/CT scans and 83.3% and 93.3% in EUS images, respectively. Another study used a Faster R-CNN model to analyze CT images from 338 pancreatic cancer patients showed high diagnostic accuracy in much less time. Additionally, two studies utilized Natural Language Processing (NLP) for identifying family histories of pancreatic cancer and detecting pancreatic cysts, with the latter achieving sensitivity and specificity rates of 99.9% and 98.8%.
Conclusions:
The current strategies for early diagnosis of pancreatic cancer focus on serum biomarkers and EUS-guided Fine Needle Aspiration (EUS-FNA) and sensitivity varies but depends on the physician's expertise. AI is showing promise in improving pancreatic cancer diagnosis by enhancing early detection and accuracy. Techniques like deep learning, NLP-based models, Faster R-CNN, and CAD systems analyze medical data and images more effectively than manual methods. AI holds the potential to shape the future of pancreatic cancer diagnosis and improve patient outcomes.