International Journal of Clinical Oncology最新文献

Background: The actual status of comprehensive genomic profiling (CGP) applications in Japan has not been clarified. We conducted a multicenter study to investigate the real-world application of CGP in gynecological malignancies.

Methods: Nine designated cancer hospitals participated in this study. Patients who underwent CGP in 2020-2021 were assigned to the CGP group (n = 134). For the population that would have been eligible for CGP, patients who received initial treatment in 2015-2016 and were either alive with disease or died of disease at 5 years follow up were included in the control group (n = 316). We compared clinicopathological characteristics including tumor type (cervix, corpus, ovary, and others including sarcoma) and age. We also investigated the context of CGP-recommended treatment.

Results: The CGP group had significantly fewer cervical cases and more others cases (cervix/corpus/ovary/others: CGP, 22/44/56/12; control, 89/79/142/6; p = 0.0003). The CGP group was significantly younger than the control group (median: CGP, 54.0; control, 65.0; p < 0.0001). Subgroup analyses revealed that patients with cervical and ovarian cancers were significantly younger in the CGP group. Among the CGP group, 17 patients (12.7%) received CGP-recommended treatments, 15 of which were not covered by public insurance. The survival time after CGP in 17 patients was longer than in the other 117 cases (median 21 vs. 11 months).

Conclusion: There was significant selection bias in tumor type and age for the application of CGP for gynecological malignancies in clinical practice in Japan. While CGP often recommended drugs not covered by public insurance, prognosis can be improved by use of CGP.

Background: Palonosetron, a second-generation 5-HT₃ receptor antagonist (5-HT₃RA), is more effective than first-generation 5-HT₃RA. Several studies have investigated whether dexamethasone (DEX), when combined with palonosetron as a 5-HT₃RA, can be spared in the delayed phase after moderately emetogenic chemotherapy (MEC). In this systematic review, we aimed to determine which between 1- and 3-day DEX administration, when combined with palonosetron, is more useful in patients receiving MEC.

Methods: The PubMed, Cochrane Library, and Ichushi-Web databases were searched for relevant studies published between 1990 and 2020. We included studies that compared the efficacy of 1- and 3-day DEX administration in preventing nausea and vomiting associated with MEC. Outcomes were "prevention of vomiting (complete response rate and no vomiting rate)," "prevention of nausea" (complete control rate, total control rate, no nausea rate, and no clinically significant nausea rate)" in the delayed phase, "prevention of blood glucose level elevation," and "prevention of osteoporosis."

Results: Eight studies were included in this systematic review. The no vomiting rate was significantly higher in the 3-day DEX group than in the 1-day DEX group. However, the other efficacy items did not significantly differ between the two groups. Meanwhile, insufficient evidence was obtained for "prevention of blood glucose level elevation" and "prevention of osteoporosis."

Conclusions: No significant differences in most antiemetic effects were found between 1- and 3-day DEX administration. Thus, DEX administration could be shortened from 3 days to 1 day when used in combination with palonosetron.

Background: Upfront androgen receptor signaling inhibitor (ARSI) along with androgen deprivation therapy is the current standard of care for metastatic castration-sensitive prostate cancer. However, evidence on second-line therapy after upfront ARSI is scarce. We aimed to evaluate the oncological outcome of ARSI versus docetaxel (DOC) after upfront ARSI therapy in a real-world clinical practice.

Methods: Subjects were metastatic castration-resistant prostate cancer (mCRPC) patients who had progressed within 2 years of upfront ARSI therapy and received ARSI (ARSI group) or DOC (DOC group) as a second-line therapy. Second-line progression-free survival (second-line PFS), and second-line overall survival (second-line OS) were assessed. Propensity score matching (PSM) was used to adjust the clinicopathological features and treatment patterns.

Results: A total of 101 mCRPC patients, 68 in the ARSI group, and 33 in the DOC group, were included in this analysis. Median second-line PFS was 6.3 months in the ARSI group and 4.9 months in the DOC group (p = 0.21). Median second-line OS was 25.0 months in the ARSI group and 14.2 months in the DOC group (p = 0.06). Prostate-specific antigen nadir ≤ 0.2 ng/ml during upfront ARSI therapy was significantly associated with improved second-line PFS. After PSM, no significant difference in second-line PFS and second-line OS were observed between the two groups.

Conclusion: ARSI or DOC has comparable oncologic outcomes in terms of second-line PFS and second-line OS. Further prospective research with longer follow-ups will be needed to identify the optimal treatment after upfront ARSI therapy.

Background: FOLFOXIRI plus bevacizumab is a standard first-line chemotherapy for patients with metastatic colorectal cancer (mCRC). However, due to the severe toxicities, this regimen is not widely used. There is limited data on the real-world efficacy and safety.

Methods: We conducted a retrospective analysis of clinical data from mCRC patients who received FOLFOXIRI plus bevacizumab as first-line chemotherapy at 31 institutions. The initial dose was standardized according to the TRIBE regimen. Induction therapy was defined as a combination of oxaliplatin, irinotecan, and fluorouracil.

Results: Out of 104 patients who met the criteria, the median age was 58 years (range, 16-72). 81% of patients had an eastern cooperative oncology group performance status (PS) of 0. An initial dose reduction was observed in 63% of patients. The median number of preplanned induction therapy cycles was 12 (range, 4-12). The completion of scheduled induction therapy cycles was observed in 45% of patients, with treatment-related toxicities being the main reason for discontinuation (63%). The median progression-free survival and overall survival were 12.8 months (95% CI, 10.6-15.0) and 27.9 months (95% CI 21.6-34.2), respectively. The objective response rate and disease control rate were 63.7% and 98.9%, respectively. The R0 resection rate was 21.2%. The main grade 3 or higher toxicities were neutropenia (51%), febrile neutropenia (10%), and nausea/vomiting (5%). No treatment-related deaths were observed.

Conclusion: In a real-world clinical setting, FOLFOXIRI plus bevacizumab demonstrated efficacy and safety comparable to previous clinical trials.

Background: Radical cystectomy in women generally includes the removal of the uterus, ovaries, and anterior vaginal wall, but the criteria for reproductive organ sparing are not clear.

Methods: A total of 2674 patients with bladder cancer were retrospectively reviewed, having undergone cystectomy at this nationwide multicenter from January 2013 to December 2019. We evaluated the incidence of malignancy in reproductive organs in a cohort of 417 women and analyzed the clinicopathological features of reproductive organ involvement. Recurrence-free survival and overall survival were reported using Kaplan-Meier survival curves.

Results: Median follow-up was 36.9 months. Of the 417 patients with urothelial carcinoma of the bladder, 325 underwent hysterectomy, and 92 had a spared uterus and anterior wall of the vagina. Twenty-nine (8.9%) patients exhibited reproductive organ involvement; this consisted of 22 (6.8%) uteri, 16 (4.9%) vaginas, and two (0.6%) ovaries. Incidental primary reproductive malignancies were found in only two (0.6%) patients. Recurrence-free survival and overall survival were significantly shorter in patients with reproductive organ involvement than in those without. Patients with reproductive organ involvement were more likely to have tumors with ≥ cT3 or sub-localization at the posterior/trigone/bladder neck.

Conclusions: The risk of reproductive organ involvement cannot be ignored in women undergoing radical cystectomy for urothelial carcinoma of the bladder, therefore, the eligibility criteria for reproductive organ preservation should be considered carefully.

Background: Lateral node metastasis confers a poor prognosis in rectal cancer. Several multidisciplinary treatments have been proposed with favorable outcomes. However, appropriate neoadjuvant/adjuvant treatments or follow-up plans based on information about the probable recurrence site have not been specified. We aimed to clarify the distinctive features of recurrence patterns for lateral node-positive low rectal cancer according to the lateral and mesorectal lymph node status.

Methods: We retrospectively analyzed 508 patients with stage III low rectal cancer who underwent lateral node dissection. We investigated the impact of lateral and mesorectal lymph node status on site-specific recurrence rates and patient survival.

Results: Analyses for relapse-free survival revealed the prognostic impact of lateral node positivity in stage III low rectal cancer (p < 0.0001). Lateral node-positive patients exhibited higher risk of overall recurrence, local recurrence, and recurrence in extra-regional nodes than lateral node-negative patients (p < 0.0001, p = 0.001, and p < 0.0001, respectively). However, lateral node positivity was not statistically associated with a hematogenous recurrence rate. In lateral node-positive patients, both tumor-node-metastasis (TNM)-N status and number of lateral nodes involved were revealed as significant prognostic factors (p < 0.0001, both). In addition, the number of lateral nodes involved could be a discriminatory indicator of probabilities of local recurrence and recurrence in extra-regional nodes (p = 0.02, and p < 0.0001, respectively).

Conclusions: Lateral node-positive low rectal cancer exhibits higher local recurrence and extra-regional node recurrence rates that correlate with the number of lateral nodes involved.

Background: Combined treatment with lenvatinib and pembrolizumab is currently regarded as one of the standard first-line therapies for advanced renal cell carcinoma (aRCC) patients. The objective of this study was to assess the efficacy and safety of this combined regimen in treatment-naïve Japanese aRCC patients.

Methods: This study included a total of 50 consecutive aRCC patients receiving combined lenvatinib plus pembrolizumab in routine clinical practice in Japan, and comprehensively analyzed clinical outcomes of this treatment.

Results: Of these 50, 7 (14.0%), 23 (46.0%) and 20 (40.0%) were classified into favorable, intermediate and poor risk groups, respectively, according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) system. Responses to this combined therapy in the 50 patients were as follows: complete response, 7 (14.0%); partial response, 26 (52.0%); stable disease, 15 (30%) and progressive disease, 2 (4%); thus, the objective response rate (ORR) was 66%. ORRs in favorable, intermediate and poor risk groups were 57.1, 69.6 and 65.0%, respectively. During the observation period, disease progression and death occurred in 14 (28.0%) and 6 (12.0%) patients, respectively, and neither the median PFS nor OS was reached. Adverse events and those corresponding to grade ≥ 3 were observed in all (100%) and 33 (66.0%) patients, respectively.

Conclusions: To our knowledge, this is the first study focusing on real-world outcomes of lenvatinib and pembrolizumab for treatment-naïve aRCC patients, showing that the efficacy and safety of this combined regimen are similar to those noted in randomized clinical trial.

Background: Imatinib therapy is the gold standard for the treatment of unresectable and metastatic gastrointestinal stromal tumors (GISTs). However, few studies have reported the long-term outcomes of the treatment.

Methods: Seventy patients who underwent imatinib therapy for unresectable and metastatic GISTs were enrolled between 2001 and 2009, and follow-up data were collected until October 2023. One hundred and sixty-eight months had passed since the final enrollment. The outcome measures were patient survival and the status of GIST and imatinib therapy. The cumulative incidence of disease progression (PD) and the chronological changes in PD hazard rate (HR) were also analyzed.

Results: The 5-, 10-, 15-, and 20-year overall survival rates were 64.3%, 30.0%, 16.8%, and 12.2%, respectively. Sixty of the 70 enrolled patients died before the data cutoff date: 47 (78.3%) patients died of GIST progression while the remaining 13 (21.7%) died of diseases other than GISTs. The cumulative incidence of PD logarithmically increased, and PD continued even after 10 years of treatment. PD HR decreased over time to reach the lowest value at 9.6 years after the initiation of treatment (HR 0.00027; 95% CI 0.00007-0.00174) and after that formed a small peak at 13 years (HR 0.00144; 95% CI 0.00043-0.00436).

Conclusions: Imatinib therapy showed high clinical efficacy in terms of long-term survival in GIST patients. However, patients undergoing imatinib therapy were at continuous risk of PD even after the 10-year treatment. Long-term treatment and follow-up beyond 10 years are necessary for unresectable and metastatic GIST patients.

Background: In metastatic clear cell renal cell carcinoma (ccRCC), recent studies have shown promising efficacy of immune checkpoint inhibitor (ICI) combination therapy. However, there are insufficient evidences about clinical efficacy and safety of ICI combination therapy in metastatic non-ccRCC (nccRCC).

Methods: We retrospectively investigated 44 patients treated with nivolumab plus ipilimumab (ICI + ICI group) or anti-PD-1/PD-L1 inhibitor plus tyrosine kinase inhibitors (TKI) (ICI + TKI group), and assessed clinical efficacy in both groups.

Results: Of all patients, overall response rate and disease control rate for ICI combination treatments were 36.3% and 75%, respectively. The median progression-free survival (PFS) and overall survival (OS) was 8.8 and 23.9 months, respectively. Multivariate analysis revealed that the presence of liver metastasis significantly affected worse PFS and OS (p = 0.035 and p = 0.049). Importantly, PFS and OS seemed similar in ICI + ICI group and ICI + TKI group (p = 0.778 and p = 0.559). Although the discontinuation rate of the combination therapy due to adverse effects in patients aged ≥ 75 years was significantly higher compared to that in patients aged < 75 years (45% versus 12%, p = 0.017), there were no significant differences in PFS and OS between two groups (p = 0.290 and p = 0.257, respectively).

Conclusion: This study confirms clinical benefit of ICI combination therapy for metastatic nccRCC patients in real-world settings. Furthermore, the effectiveness of combination therapy was comparable between patients aged < 75 and those ≥75 years with respect to clinical prognosis.

Background: Colorectal cancer (CRC) is a major global health concern, with a rising incidence in young individuals. Early-onset CRC displays unique clinicopathological and molecular characteristics, necessitating a closer examination of prognosis, particularly in the context of adjuvant chemotherapy. This study aimed to investigate the prognosis of early-onset CRC patients (< 50 years) diagnosed at stage II/III compared to older counterparts, utilizing propensity score matching to minimize heterogeneity.

Methods: A retrospective analysis of 3324 stage II/III CRC patients aged < 70 years was conducted, focusing on age-based subgroups (< 50 vs. ≥ 50 years). Propensity score matching balanced clinical characteristics. Relapse-free survival (RFS) and overall survival (OS) were analyzed.

Results: In stage II CRC, age of onset did not impact prognosis after adjuvant chemotherapy, with no significant differences in RFS (5-year RFS rates: 80% in both groups, p = 0.98) and OS (5-year OS rates: 96% vs. 92%, p = 0.17). In stage III, a trend suggested slightly poorer OS in patients aged < 50 years than those ≥ 50 years (5-year OS rates: 85% vs. 88%, p = 0.077). However, in a propensity score-matched cohort, age-dependent differences were attenuated (5-year OS rates: 85% vs. 88%, p = 0.32).

Conclusion: In the context of stage II/III CRC patients receiving adjuvant chemotherapy, age was not an independent predictor of prognosis. Age alone should not be the sole factor guiding treatment decisions.