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17 pages, 1519 KiB

Open AccessArticle

BRAF V600E and Non-V600E Mutations in RAS Wild-Type Metastatic Colorectal Cancer: Prognostic and Therapeutic Insights from a Nationwide, Multicenter, Observational Study (J-BROS)

by Hiroya Taniguchi, Kay Uehara, Toshiaki Ishikawa, Osamu Okochi, Naoya Akazawa, Hiroyuki Okuda, Hiroko Hasegawa, Manabu Shiozawa, Masato Kataoka, Hironaga Satake, Takaya Shimura, Chihiro Kondoh, Hidekazu Kuramochi, Toshihiko Matsumoto, Naoki Takegawa, Toshifumi Yamaguchi, Michitaka Nagase, Masato Nakamura, Nao Takano, Hideto Fujita, Takanori Watanabe, Tomohiro Nishina, Yasuhiro Sakamoto, Toshikazu Moriwaki, Hisatsugu Ohori, Masayoshi Nakanishi, Yosuke Kito, Setsuo Utsunomiya, Takeshi Ishikawa, Dai Manaka, Hiroshi Matsuoka, Takeshi Suto, Toshiyuki Arai, Shinichiro Shinzaki, Tohru Funakoshi, Goro Nakayama, Yuji Negoro, Yasushi Tsuji, Akitaka Makiyama, Kunio Takuma, Atsuki Arimoto, Katsunori Shinozaki, Ayako Mishima and Toshiki Masuishi Show full author list Hide full author list

Cancers 2025, 17(3), 399; https://doi.org/10.3390/cancers17030399 - 25 Jan 2025

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Abstract

Background/Objectives: BRAF mutations occur in 5–10% of metastatic colorectal cancer (mCRC) cases, but their implications for prognosis and optimal treatment remain unclear. Methods: This multicenter, prospective observational study analyzed 377 RAS wild-type cases from 511 patients across 32 centers, using PCR-based methods. Results: [...] Read more.

Background/Objectives: BRAF mutations occur in 5–10% of metastatic colorectal cancer (mCRC) cases, but their implications for prognosis and optimal treatment remain unclear. Methods: This multicenter, prospective observational study analyzed 377 RAS wild-type cases from 511 patients across 32 centers, using PCR-based methods. Results: BRAF mutations were identified in 21% (79/377) of cases, predominantly V600E (89.9%) with a minority of non-V600E (10.1%). Microsatellite instability (MSI) testing revealed MSI-high in 11.3%, exclusively among V600E cases. V600E mutations were linked to right-sided tumors, poor differentiation, and elevated CA19-9 levels. Median survival was significantly lower in V600E cases compared to BRAF wild-type (12.4 vs. 37.5 months, HR 3.25, p < 0.001) and marginally lower non-V600E cases (12.4 vs. 34.7 months, HR 0.61, p = 0.057). Chemotherapy regimens (doublet vs. triplet) and targeted treatments (bevacizumab vs. anti-EGFR) showed no significant survival differences in V600E patients. Similarly, RAS/BRAF wild-type patients had comparable survival with bevacizumab versus anti-EGFR, even for left-sided tumors. Conclusions: These findings highlight distinct clinical and prognostic profiles for BRAF V600E and non-V600E mutations, while treatment choice appears to have limited impact on survival in these subgroups or RAS/BRAF wild-type cases. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research and Initiatives in Japan)

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12 pages, 2047 KiB

Open AccessArticle

The Prognostic Impact of Adipophilin Expression on Long-Term Survival Following Liver Resection in Patients with Colorectal Liver Metastases

by Tung Thanh Lai, Mitsuaki Ishida, Hisashi Kosaka, Kosuke Matsui, Hideyuki Matsushima, Hidekazu Yamamoto, Gozo Kiguchi, Khanh Van Nguyen, Kyoko Inoue, Moriyasu Takada, Hiroki Kato, Yoshinobu Hirose, Kengo Yoshii and Masaki Kaibori

Cancers 2024, 16(22), 3827; https://doi.org/10.3390/cancers16223827 - 14 Nov 2024

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Abstract

Background/Objectives: Adipophilin (ADP) is a protein associated with lipid droplets, and its expression is related to poor prognosis in certain cancers. However, its impact on the survival of patients with colorectal liver metastases (CRLMs) remains unclear. This study investigated the impact of [...] Read more.

Background/Objectives: Adipophilin (ADP) is a protein associated with lipid droplets, and its expression is related to poor prognosis in certain cancers. However, its impact on the survival of patients with colorectal liver metastases (CRLMs) remains unclear. This study investigated the impact of ADP expression on long-term survival following hepatectomy in patients with CRLM. Methods: We retrospectively analyzed 102 consecutive patients who underwent hepatectomy between 2006 and 2022. ADP expression was examined in resected specimens through immunohistochemical staining using tissue microarrays. Long-term outcomes for ADP-positive (n = 51) and ADP-negative (n = 51) groups were compared with Kaplan–Meier survival analysis. Results: We found significantly decreased 5-year recurrence-free survival (RFS) and overall survival (OS) rates for ADP-positive patients relative to ADP-negative patients (29.4% versus 52.1%, respectively; p = 0.001 and 43.7% versus 72.2%, respectively; p = 0.003). Moreover, multivariate Cox hazards analysis demonstrated that patients with ADP-positive CRLM had a worse prognosis after hepatectomy than those with ADP-negative CRLM, as reflected by both RFS (HR 2.46, 95% CI 1.39–4.36, p = 0.002) and OS (HR: 2.89, 95% CI 1.43–5.85, p = 0.003). Conclusions: ADP expression had a significant prognostic impact on the survival of patients with CRLM following liver resection and may aid in optimal treatment planning. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research and Initiatives in Japan)

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11 pages, 1197 KiB

Open AccessArticle

C-Reactive Protein-to-Albumin Ratio as a Predictive Indicator for Evaluating Tolerability in S-1 Adjuvant Chemotherapy after Curative Surgery for Pancreatic Cancer: An External Validation Cohort Study

by Naotake Funamizu, Shozo Mori, Akimasa Sakamoto, Miku Iwata, Mikiya Shine, Chihiro Ito, Mio Uraoka, Yoshitomo Ueno, Kei Tamura, Yuzo Umeda, Taku Aoki and Yasutsugu Takada

Cancers 2024, 16(19), 3372; https://doi.org/10.3390/cancers16193372 - 1 Oct 2024

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Abstract

Background: S-1 in adjuvant chemotherapy (AC) administration after pancreatic cancer (PC) surgery has been standardized in Japan. The Ehime study confirmed that a postoperative higher C-reactive protein-to-albumin ratio (CAR) value predicted the risk of adverse event (AE)-related S-1 non-completion as an AC in [...] Read more.

Background: S-1 in adjuvant chemotherapy (AC) administration after pancreatic cancer (PC) surgery has been standardized in Japan. The Ehime study confirmed that a postoperative higher C-reactive protein-to-albumin ratio (CAR) value predicted the risk of adverse event (AE)-related S-1 non-completion as an AC in patients with PC after curative surgery. This study aimed to investigate the index to predict S-1 tolerance among patients who underwent curative surgery for PC (the Dokkyo study). Methods: This retrospective validation cohort study included 172 patients at the Department of Hepato-Biliary Pancreatic Surgery, Dokkyo Medical University, Japan, from January 2010 to December 2022. All patients underwent nutritional screening using the postoperative CAR. S-1 completion status and its effect on prognosis were systematically followed up and investigated. We conducted a statistical analysis of predictive markers to investigate their association with S-1 completion. Results: Patients were categorized into the S-1 completion (N = 91) and non-completion (N = 81) groups. The S-1 completion group demonstrated a significantly lower CAR than the S1 non-completion group. Moreover, the current study revealed a significant difference in the S-1 completion rate, applying the CAR cutoff value of 0.05 established in the Ehime study. Additionally, univariate and multivariate analyses confirmed that a CAR of <0.05 was significantly associated with S-1 completion. Conclusions: The Dokkyo study confirmed the results observed in the Ehime study. Consequently, an increased postoperative CAR value appeared as a universal applicable marker for the risk factor of AE-related S-1 non-completion after curative surgery for patients with PC. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research and Initiatives in Japan)

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13 pages, 2079 KiB

Open AccessArticle

Long-Term Outcomes of Ablative Carbon-Ion Radiotherapy for Central Non-Small Cell Lung Cancer: A Single-Center, Retrospective Study

by Shuri Aoki, Hitoshi Ishikawa, Mio Nakajima, Naoyoshi Yamamoto, Shinichiro Mori, Masaru Wakatsuki, Noriyuki Okonogi, Kazutoshi Murata, Yuji Tada, Teruaki Mizobuchi, Ichiro Yoshino and Shigeru Yamada

Cancers 2024, 16(5), 933; https://doi.org/10.3390/cancers16050933 - 25 Feb 2024

Cited by 1 | Viewed by 2089

Abstract

The aim of this study is to assess the efficacy and safety of ablative carbon ion radiotherapy (CIRT) for early stage central non-small cell lung cancer (NSCLC). We retrospectively reviewed 30 patients who had received CIRT at 68.4 Gy in 12 fractions for [...] Read more.

The aim of this study is to assess the efficacy and safety of ablative carbon ion radiotherapy (CIRT) for early stage central non-small cell lung cancer (NSCLC). We retrospectively reviewed 30 patients who had received CIRT at 68.4 Gy in 12 fractions for central NSCLC in 2006–2019. The median age was 75 years, and the median Karnofsky Performance Scale score was 90%. All patients had concomitant chronic obstructive pulmonary disease, and 20 patients (67%) were considered inoperable. In DVH analysis, the median lung V5 and V20 were 15.5% and 10.4%, and the median Dmax, D0.5cc, D2cc of proximal bronchial tree was 65.6 Gy, 52.8 Gy, and 10.0 Gy, respectively. At a median follow-up of 43 months, the 3-year overall survival, disease-specific survival, and local control rates were 72.4, 75.8, and 88.7%, respectively. Two patients experienced grade 3 pneumonitis, but no grade ≥3 adverse events involving the mediastinal organs occurred. Ablative CIRT is feasible and effective for central NSCLC and could be considered as a treatment option, especially for patients who are intolerant of other curative treatments. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research and Initiatives in Japan)

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11 pages, 2187 KiB

Open AccessArticle

Risk Factors for Bleeding Events in Japanese Patients with Advanced Lung Cancer: Data from the Rising-VTE/NEJ037 Study

by Keita Kawakado, Yukari Tsubata, Takamasa Hotta, Masahiro Yamasaki, Nobuhisa Ishikawa, Kazunori Fujitaka, Tetsuya Kubota, Kunihiko Kobayashi and Takeshi Isobe

Cancers 2024, 16(2), 301; https://doi.org/10.3390/cancers16020301 - 10 Jan 2024

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Abstract

Despite the occurrence of various hemorrhagic events during advanced lung cancer treatment, few researchers have reported on their risk factors. Moreover, the development of cancer-related thromboembolism indicates anticoagulant use. However, adverse events such as bleeding should be monitored. In this study, we aimed [...] Read more.

Despite the occurrence of various hemorrhagic events during advanced lung cancer treatment, few researchers have reported on their risk factors. Moreover, the development of cancer-related thromboembolism indicates anticoagulant use. However, adverse events such as bleeding should be monitored. In this study, we aimed to identify factors that influence the onset of hemorrhagic events in patients with lung cancer. The Rising-VTE/NEJ037 study was a multicenter, prospective, observational study. A total of 1008 patients with lung cancer who were unsuitable for radical resection or radiation were enrolled and followed up for 2 years. Multivariate analysis using a Cox proportional hazard model was performed to compare the outcomes of the time to the onset of hemorrhagic events for 2 years after registration. Hemorrhagic events occurred in 115 patients (11.4%), with 35 (30.4%) experiencing major bleeding. Significant risk factors included venous thromboembolism (VTE) (hazard ratio [HR]: 4.003, p < 0.001) and an Eastern Cooperative Oncology Group Performance Status score of 1 (HR: 2.476, p < 0.001). Factors that significantly reduced hemorrhagic event risk were female sex (HR: 0.454, p = 0.002) and M1a status (HR: 0.542, p = 0.038). VTE is a risk factor for hemorrhagic events in patients with advanced lung cancer, and risks associated with anticoagulant therapy should be considered. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research and Initiatives in Japan)

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11 pages, 1842 KiB

Open AccessArticle

Prognostic Factors for Resolution Delay of Lower Urinary Tract Symptoms in Patients with Prostate Cancer after Low-Dose-Rate Brachytherapy

by Tomoki Taniguchi, Makoto Kawase, Keita Nakane, Masahiro Nakano, Koji Iinuma, Daiki Kato, Manabu Takai, Yuki Tobisawa, Takayuki Mori, Hirota Takano, Tomoyasu Kumano, Masayuki Matsuo, Takayasu Ito and Takuya Koie

Cancers 2023, 15(16), 4048; https://doi.org/10.3390/cancers15164048 - 10 Aug 2023

Cited by 2 | Viewed by 1348

Abstract

Urinary storage symptoms after low-dose-rate brachytherapy (LDR-BT) with iodine-125 have been noted to be less likely to improve to baseline compared to voiding symptoms. This study aimed to evaluate the chronological changes in the overactive bladder symptom score (OABSS) and the time-to-resolution of [...] Read more.

Urinary storage symptoms after low-dose-rate brachytherapy (LDR-BT) with iodine-125 have been noted to be less likely to improve to baseline compared to voiding symptoms. This study aimed to evaluate the chronological changes in the overactive bladder symptom score (OABSS) and the time-to-resolution of OABSS in patients undergoing LDR-BT. Patients with prostate cancer who underwent LDR-BT at Gifu University Hospital were enrolled. The OABSS was evaluated before and after LDR-BT. Patients were divided into the OABSS resolution and resolution delay groups, and the association between OABSS resolution delay and clinicopathological covariates was evaluated. In total, 237 patients were enrolled in this study, with a median follow-up of 88.3 months. The OABSS in both groups worsened at 3 months following operation and gradually recovered at 9 months; however, the OABSS in the resolution delay group tended to worsen again after that. In the multivariate analysis, preoperative OABSS and the change from baseline to maximal OABSS were associated with OABSS resolution. To our knowledge, this is the first study to evaluate the delayed resolution of OABSS after LDR-BT in patients with prostate cancer. A low baseline OABSS and significant changes in the OABSS from baseline were independent predictors of delayed OABSS resolution. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research and Initiatives in Japan)

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11 pages, 2608 KiB

Open AccessEditor’s ChoiceArticle

Clinical Possibility of Caenorhabditis elegans as a Novel Evaluation Tool for Esophageal Cancer Patients Receiving Chemotherapy: A Prospective Study

by Yuta Sato, Manabu Futamura, Yoshihiro Tanaka, Hiroshi Tsuchiya, Masahiro Fukada, Toshiya Higashi, Itaru Yasufuku, Ryuichi Asai, Jesse Yu Tajima, Shigeru Kiyama, Hideyuki Hatakeyama, Masayo Morishita, Takaaki Hirotsu, Eric di Luccio, Takuma Ishihara, Nobuhisa Matsuhashi and Kazuhiro Yoshida

Cancers 2023, 15(15), 3870; https://doi.org/10.3390/cancers15153870 - 29 Jul 2023

Cited by 4 | Viewed by 3625

Abstract

Background: The nematode Caenorhabditis elegans (C. elegans) possesses a sophisticated sense of smell and is used for a novel cancer screening test that utilizes the chemotaxis index. We designed a single-institution, prospective study to confirm the ability of Nematode Nose (N-NOSE) [...] Read more.

Background: The nematode Caenorhabditis elegans (C. elegans) possesses a sophisticated sense of smell and is used for a novel cancer screening test that utilizes the chemotaxis index. We designed a single-institution, prospective study to confirm the ability of Nematode Nose (N-NOSE) to determine preoperative chemotherapy’s efficacy for esophageal cancer patients. Patients and Methods: We investigated the predictability of N-NOSE screening for the clinical effects of preoperative chemotherapy for esophageal cancer patients receiving radical surgery. The index reduction score (IRS) was calculated via the chemotaxis of C. elegans at three points: before treatment, before surgery, and after surgery, and its clinical relevance was examined. Result: Thirty-nine patients with esophageal cancer were enrolled from August 2020 to December 2021, and 30 patients receiving radical surgery were examined. Complete response or partial response was achieved in 23 cases (76.7%). When the target of the treatment effect was complete response only, the prediction accuracies of the IRS calculated by area under the curve was 0.85 (95% Confidence interval: 0.62–1) in clinically achieving complete response group, and the sensitivity and specificity were 1 and 0.63, respectively. Conclusion: Index reduction score using N-NOSE screening may reflect the efficacy of chemotherapy for esophageal cancer patients. A large-scale prospective study at multiple centers is desired in the future. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research and Initiatives in Japan)

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Review

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13 pages, 3550 KiB

Open AccessReview

KRAS^G12C Inhibitor as a Treatment Option for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia

by Kazushi Fujimoto, Satoshi Ikeda, Erina Tabata, Taichi Kaneko, Shinobu Sagawa, Chieri Yamada, Kosumi Kumagai, Takashi Fukushima, Sanshiro Haga, Masayuki Watanabe, Tatsuya Muraoka, Akimasa Sekine, Tomohisa Baba and Takashi Ogura

Cancers 2024, 16(7), 1327; https://doi.org/10.3390/cancers16071327 - 28 Mar 2024

Cited by 3 | Viewed by 2930

Abstract

Non-small-cell lung cancer (NSCLC) with comorbid interstitial pneumonia (IP) is a population with limited treatment options and a poor prognosis. Patients with comorbid IP are at high risk of developing fatal drug-induced pneumonitis, and data on the safety and efficacy of molecularly targeted [...] Read more.

Non-small-cell lung cancer (NSCLC) with comorbid interstitial pneumonia (IP) is a population with limited treatment options and a poor prognosis. Patients with comorbid IP are at high risk of developing fatal drug-induced pneumonitis, and data on the safety and efficacy of molecularly targeted therapies are lacking. KRAS mutations have been frequently detected in patients with NSCLC with comorbid IP. However, the low detection rate of common driver gene mutations, such as epidermal growth factor receptor and anaplastic lymphoma kinase, in patients with comorbid IP frequently results in inadequate screening for driver mutations, and KRAS mutations may be overlooked. Recently, sotorasib and adagrasib were approved as treatment options for advanced NSCLC with KRAS^G12C mutations. Although patients with comorbid IP were not excluded from clinical trials of these KRAS^G12C inhibitors, the incidence of drug-induced pneumonitis was low. Therefore, KRAS^G12C inhibitors may be a safe and effective treatment option for NSCLC with comorbid IP. This review article discusses the promise and prospects of molecular-targeted therapies, especially KRAS^G12C inhibitors, for NSCLC with comorbid IP, along with our own clinical experience. Full article

(This article belongs to the Special Issue Oncology: State-of-the-Art Research and Initiatives in Japan)

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