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The efficacy of neoadjuvant therapy (NT) versus surgery first (SF) for pancreatic ductal adenocarcinoma (PDAC) remains controversial. A random-effects meta-analysis of only prospective randomized controlled trials (RCTs) comparing NT versus SF for potentially resectable (PR) or borderline resectable (BR) PDAC was performed. Among six RCTs including 850 patients, 411 (48.3%) received NT and 439 (51.6%) SF. In all included trials, NT was gemcitabine-based: four using chemoradiation and two chemotherapy alone. Based on an intention-to-treat analysis, NT resulted in improved overall survival (OS) compared to SF (HR 0.73, 95% CI 0.61–0.86). This effect was independent of anatomic classification (PR: hazard ratio (HR) 0.73, 95% CI 0.59–0.91; BR: HR 0.51 95% CI 0.28–0.93) or NT type (chemoradiation: HR 0.77, 95% CI 0.61–0.98; chemotherapy alone: HR 0.68, 95% CI 0.54–0.87). Overall resection rate was similar (risk ratio (RR) 0.93, 95% CI 0.82–1.04, I2 = 39.0%) but NT increased the likelihood of a margin-negative (R0) resection (RR 1.51, 95% CI 1.18–1.93, I2 = 0%) and having negative lymph nodes (RR 2.07, 95% CI 1.47–2.91, I2 = 12.3%). In this meta-analysis of prospective RCTs, NT significantly improved OS in an intention-to-treat fashion, compared with SF for localized PDAC. Randomized controlled trials using contemporary multi-agent chemotherapy will be needed to confirm these findings and to define the optimal NT regimen.

Background The Cancer Staging Manual , 8th edition, now includes post-neoadjuvant therapy (ypTNM) staging for gastric cancer patients. Our purpose was to determine whether the tumor regression grade (TRG) of the primary tumor is useful for predicting the survival of these patients. Methods We performed a retrospective review of an institutional database and identified patients with clinically non-metastatic gastric adenocarcinoma who underwent preoperative chemotherapy or chemoradiation therapy before gastrectomy. Pathology reports were reviewed, and TRG was classified as follows: 0 (complete response), 1 (viable tumor cells ≤ 1–2%), 2 (viable cells ≤ 50%), or 3 (viable cells > 50%). Results Of the 356 patients identified, including 80 (23%) with a gastroesophageal junction tumor, 268 (75%) had undergone preoperative chemoradiation therapy. Fifty-six (16%) had TRG 0, 57 (16%) TRG 1, 128 (36%) TRG 2, and 115 (32%) TRG 3. No association between TRG and pretreatment factors was identified, except for signet-ring cell histologic type and tumor location. A higher TRG was associated with more advanced ypT and ypN categories (both p  < 0.001), ypM1 ( p  = 0.004), and R1 resection ( p  = 0.052). The median overall survival (OS) duration was 6.6 years, and the 5-year OS rate was 54.1%. TRG 3 was associated with a shorter OS duration than were other TRG scores ( p  = 0.015), while the OS did not differ significantly among the TRG 0–2 groups ( p  = 0.803). On multivariable analysis, TRG was not associated with OS after adjustment for ypN status. Conclusion In gastric cancer patients who underwent preoperative therapy, TRG 3 was associated with advanced ypStage and R1 resection. Patients with TRG 3 had a shorter OS duration because of associated advanced ypStage, particularly ypN+ status.

With recent advances in pancreatic imaging and surgical techniques, a distinct subset of pancreatic tumors is emerging that blurs the distinction between resectable and locally advanced disease: tumors of \"borderline resectability.\" In our practice, patients with borderline-resectable pancreatic cancer include those whose tumors exhibit encasement of a short segment of the hepatic artery, without evidence of tumor extension to the celiac axis, that is amenable to resection and reconstruction; tumor abutment of the superior mesenteric artery involving <180 degrees of the circumference of the artery; or short-segment occlusion of the superior mesenteric vein, portal vein, or their confluence with a suitable option available for vascular reconstruction because the veins are normal above and below the area of tumor involvement. With currently available surgical techniques, patients with borderline-resectable pancreatic head cancer are at high risk for a margin-positive resection. Therefore, our approach to these patients is to use preoperative systemic therapy and local-regional chemoradiation to maximize the potential for an R0 resection and to avoid R2 resections. In our experience, patients with favorable responses to preoperative therapy (radiographical evidence of tumor regression and improvement in serum tumor marker levels) are the subset of patients who have the best chance for an R0 resection and a favorable long-term outcome.

Abstract Background A pathological complete response (pCR) following neoadjuvant chemoradiation (CRT) is associated with a favorable prognosis in patients with locally advanced rectal cancer. Patients with metastatic colorectal cancer (mCRC) often receive systemic therapy, and some patients undergo primary tumor resection after preoperative therapy. However, whether oncological outcomes remain favorable in patients with mCRC and pCR in the primary tumor site (ypT0N0M1) following preoperative therapy is unknown. Patients and methods Patients with mCRC who underwent preoperative therapy followed by primary tumor resection between March 2014 and August 2023, and in whom pCR was confirmed at the primary tumor site, were retrospectively included in this study. The outcome variables investigated were patient demographics, overall survival (OS), and progression-free survival (PFS). Results We included 57 patients who met the inclusion criteria. The median follow-up was 27.1 (range, 7.9-120.6) months. The 2-year PFS and 3-year OS rates in all the patients were 62.2% and 84.5%, respectively. Patients with a primary tumor site in the colon (n = 29) had superior OS (P = 0.039) and a trend toward superior PFS (P = .149) compared to those with a primary site in the rectum (n = 28). Conclusion Patients with mCRC following preoperative therapy, particularly those with colon cancer, who experienced a pCR in the primary tumor site have a favorable prognosis.

Background The oral gonadotropin-releasing hormone antagonist relugolix, which temporarily stops menstruation, is used to treat heavy menstrual bleeding, pelvic pressure, and low back pain in women with uterine fibroids. Treatment can also help women recover from low hemoglobin levels and possibly shrink the fibroids. However, evidence of preoperative use of relugolix before laparoscopic myomectomy is limited. Nevertheless, the treatment could reduce interoperative blood loss, decrease the risk of developing postoperative anemia, and shorten the operative time. Thus, we aim to test whether 12-week preoperative treatment with relugolix (40 mg orally, once daily) is similar to or not worse than leuprorelin (one injection every 4 weeks) to reduce intraoperative blood loss. Methods Efficacy and safety of preoperative administration of drugs will be studied in a multi-center, randomized, open-label, parallel-group, noninferiority trial enrolling premenopausal women ≥ 20 years of age, diagnosed with uterine fibroids and scheduled for laparoscopic myomectomy. Participants ( n  = 80) will be recruited in the clinical setting of participating institutions. The minimization method (predefined factors: presence or absence of fibroids ≥ 9 cm and the International Federation of Gynecology and Obstetrics [FIGO] type 1–5 fibroids) with randomization is used in a 1:1 allocation. Relugolix is a 40-mg oral tablet taken once a day before a meal, for 12 weeks, up to the day before surgery. Leuprorelin is a 1.88 mg, or 3.75 mg subcutaneous injection, given in three 4-week intervals during patient visits before the surgery. For the primary outcome measure of intraoperative bleeding, the blood flow is collected from the body cavity, surgical sponges, and collection bag and measured in milliliters. Secondary outcome measures are hemoglobin levels, myoma size, other surgical outcomes, and quality-of-life questionnaire responses (Kupperman Konenki Shogai Index and Uterine Fibroid Symptoms—Quality of Life). Discussion Real-world evidence will be collected in a clinical setting to use pre-treatment with an oral gonadotropin-releasing hormone antagonist to reduce intraoperative bleeding in women who undergo laparoscopic myomectomy. Trial registration jRCTs031210564 was registered on 19 January 2022 in the Japan Registry of Clinical Trials ( https://jrct.niph.go.jp ).

Background Both Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. We analyzed the consistency of TRG and RECIST 1.1 for gastric cancer (GC) patients and compared their prognostic values. Methods Patients with GC who received preoperative chemotherapy or chemoimmunotherapy and had records of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0–1 and 2–3 are considered as corresponding to complete response (CR)/partial response (PR) and stable disease (SD)/progress disease (PD) in RECIST 1.1, respectively. The primary endpoints were disease-free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Survival analysis was performed using the Kaplan Meier method. Result One hundred fifty seven GC patients were enrolled, including 125 with preoperative chemotherapy and 32 with chemoimmunotherapy. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results between RECIST 1.1 and TRG. TRG was correlated with both OS and DFS ( P  = 0.02 and 0.03, respectively) while response according to RECIST1.1 was not ( P  = 0.86 and 0.23, respectively). The median DFS had not reached in the TRG 0–1 group and was 16.13 months in TRG 2–3 group. TRG 2–3 was associated with young age and peritoneal or liver metastasis. Besides, preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone (34.4% vs 8.0%, P  < 0.001). Conclusion TRG was in poor agreement with RECIST 1.1. TRG was better than RECIST 1.1 in predicting DFS and OS for GC patients who received preoperative therapy.

BackgroundWhether the addition of trastuzumab to chemo(immuno)therapy for the preoperative treatment of patients with potentially resectable HER2-positive gastric cancer has clinical benefits remains to be explored. This real-world observational study was designed to evaluate the efficacy and safety of trastuzumab plus chemo(immuno)therapy for neoadjuvant or conversion therapy in patients with potentially resectable HER2-positive gastric cancer.MethodsWe retrospectively collected the clinical data of treatment-naïve patients with potentially resectable stage III to IVB HER2-positive gastric cancer who received preoperative therapy prior to D2 gastrectomy. The main outcomes of interest included tumour regression grade (TRG), treatment-related adverse events (TRAEs), and event-free survival (EFS).ResultsA total of 40 patients were included in the analysis, specifically, 27 patients (67.5%, 95% CI 0.520-0.799) received preoperative trastuzumab plus chemo(immuno)therapy, and 13 patients (32.5%, 95% CI 0.201-0.480) received chemo(immuno)therapy. All these patients subsequently underwent D2 gastrectomy. Regarding surgical outcomes, TRG0/1 rates were 33.3% (95% CI 0.186-0.522) in the trastuzumab-containing treatment group and 15.4% (95% CI 0.043-0.422) in the chemotherapy/chemoimmunotherapy group. Regarding safety, 66.7% (95% CI 0.478-0.814) of patients in the trastuzumab-containing treatment group and 61.5% (95% CI 0.355-0.823) of patients in the chemotherapy/chemoimmunotherapy group experienced preoperative TRAEs. The probabilities of EFS were not statistically significant between the two groups by the last follow-up.ConclusionAdditions of trastuzumab to preoperative chemotherapy or chemoimmunotherapy resulted in a TRG0/1 rate of 33.3% among patients with potentially resectable HER2-positive gastric cancer, and the combined regimen exhibited a favourable safety profile.

Pancreatic cancer is one of the most lethal of all malignancies. One of the reasons for the dismal prognosis is that most diagnoses are made when the disease is either locally advanced or metastatic. Recent advances in chemotherapy and chemoradiotherapy (CRT) enable “conversion surgery” to be performed for selected patients with initially unresectable pancreatic cancer following favorable responses to preoperative treatment. Using FOLFIRINOX as preoperative treatment, the resection rate was reported as 6–44% of patients with locally advanced cancer and the prognosis of these patients was favorable. Even for metastasized cancer, recent reports show the effectiveness of conversion surgery, which has achieved 27–56 months of median overall survival. However, there are many unanswered questions about conversion surgery. The optimal regimen and duration of preoperative treatment remain unclear and there is still debate regarding the safety and effectiveness of vascular resection, which is often required for curative resection of locally advanced cancer. Accumulation of more data on conversion surgery is required to establish the safety and effectiveness of this treatment. In this review, we summarize the current status and unresolved issues about conversion surgery for initially unresectable pancreatic cancer.

Abstract Introduction: The phase III REFLECT trial demonstrated that lenvatinib was superior to sorafenib in terms of progression-free survival (PFS), time to progression, and objective response rate (ORR) for patients with unresectable hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of preoperative lenvatinib therapy for patients with oncologically or technically unresectable HCC. Methods: In this multicenter single-arm phase II trial, patients with advanced HCC and factors suggestive of a poor prognosis (macroscopic vascular invasion, extrahepatic metastasis, or multinodular tumors) were enrolled. Patients with these factors, even with technically resectable HCC, were defined as oncologically unresectable because of the expected poor prognosis after surgery. After 8 weeks of lenvatinib therapy, the patients were assessed for resectability, and tumor resection was performed if the tumor was considered technically resectable. The primary endpoint was the surgical resection rate. The secondary endpoints were the macroscopic curative resection rate, overall survival (OS), ORR, PFS, and the change in the indocyanine green retention rate at 15 min as measured before and after lenvatinib therapy. The trial was registered with the Japan Registry of Clinical Trials (s031190057). Results: Between July 2019 and January 2021, 49 patients (42 oncologically unresectable patients and 7 technically unresectable patients) from 11 centers were enrolled. The ORR was 37.5% based on mRECIST and 12.5% based on RECIST version 1.1. Thirty-three patients underwent surgery (surgical resection rate: 67.3%) without perioperative mortality. The surgical resection rate was 76.2% for oncologically unresectable patients and 14.3% for technically unresectable patients. The 1-year OS rate and median PFS were 75.9% and 7.2 months, respectively, with a median follow-up period of 9.3 months. Conclusions: The relatively high surgical resection rate seen in this study suggests the safety and feasibility of lenvatinib therapy followed by surgical resection for patients with oncologically or technically unresectable HCC.

When preoperative radiotherapy (RT) is best used in rectal cancer is subject to discussions and guidelines differ. To understand the selection mechanisms, we analysed treatment decisions in all patients diagnosed between 2010–2020 in two Swedish regions (Uppsala with a RT department and Dalarna without). Information on staging and treatment (direct surgery, short-course RT, or combinations of RT/chemotherapy) in the Swedish Colorectal Cancer Registry were used. Staging magnetic resonance imaging (MRI) permitted a division into risk groups, according to national guidelines. Logistic regression explored associations between baseline characteristics and treatment, while Cohen’s kappa tested congruence between clinical and pathologic stages. A total of 1150 patients without synchronous metastases were analysed. Patients from Dalarna were older, had less advanced tumours and were pre-treated less often (52% vs. 63%, p < 0.001). All MRI characteristics (T-/N-stage, MRF, EMVI) and tumour levels were important for treatment choice. Age affected if chemotherapy was added. The correlation between clinical and pathological T-stage was fair/moderate and poor for N-stage. The MRI-based risk grouping influenced treatment choice the most. Since the risk grouping was modified to diminish the pre-treated proportion, fewer patients were irradiated with time. MRI staging is far from optimal. A stronger wish to decrease irradiation may explain why fewer patients from Dalarna were irradiated, but inequality in health care cannot be ruled out.