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ABSTRACT Various studies have reported resistance mechanisms and treatment methods after epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitor treatment; however, treatment policies have not yet been established, and few cases have reported transformation to pleomorphic carcinoma (PC) as the resistance mechanism. Herein, we report the case of a 66‐year‐old woman who was diagnosed with Stage 4A lung adenocarcinoma (cT2bN0M1b) through bronchoscopic biopsy. Genetic profiling revealed an EGFR L858R mutation; therefore, osimertinib was administered as the first‐line therapy and achieved a partial response. After 46 months of osimertinib treatment, the metastases remained under control; however, the primary tumor enlarged and was therefore resected. Pathological examination confirmed the diagnosis of PC. Genetic testing of the surgical pathology specimen showed that the EGFR mutation L858R was retained, and the patient was considered drug‐resistant owing to the histologic transformation to PC. The patient continued osimertinib therapy and had no recurrence at 9 months postoperatively. Transformation to PC following osimertinib administration is rare, and we report this unique case. This study was approved by the Jichi Medical University Saitama Medical Center Ethics Committee (S24‐073), and written informed consent was obtained from the patient. [ABSTRACT FROM AUTHOR]

Aim: To investigate the impact of pentoxifylline (PTX, 3 × 400 mg per day) and ursodeoxycholic acid (UDCA, 3 × 250 mg per day) administered for 12 weeks on radiation-induced liver toxicity. Materials and methods: Inclusion criteria were liver metastases of extrahepatic malignancies undergoing HDR-BT. 36 patients were prospectively randomized to the medication (N = 18) or control arm (N = 18) and follow-up by hepatobiliary magnetic resonance imaging (MRI) was scheduled 6 and 12 weeks after local ablation by HDR-BT. We determined the threshold doses of fRILI by image fusion of MRI with the dosimetry data. Results: 32 patients completed the study schedule. Per-protocol treatment was limited to 8 patients in the medication group and 16 patients in the control group. 22 adverse events of any grade likely or certainly related to PTX were recorded in 12 patients leading to the discontinuation of the study medication in 7 patients and to a dose reduction of PTX in 2 patients. In the per-protocol population, statistical analysis failed to prove a reduction of fRILI 6 and 12 weeks after HDR-BT. The incidence of adverse effects attributed to PTX (70.6%) was well above the data found in the literature for its approved indication. Conclusion: The study endpoint was not met mainly attributed to the low statistical power of the small per-protocol cohort. Independently, PTX cannot be recommended for the reduction of radiation-induced liver toxicity in oncologic patients undergoing HDR-BT of liver metastases. Further studies might focus on a combination of UDCA with other potential drugs to help establish a preventive and tolerable regimen. [ABSTRACT FROM AUTHOR]

Background: Age-standardized mortality rates for metastatic colorectal cancer (mCRC) are highest among elderly patients. In current clinical guidelines, treatment recommendations for this patient population are based on a limited number of clinical trials. Patients and methods: In this monocentric, retrospective analysis we characterized patients aged =70 years undergoing systemic therapy for mCRC and overall survival (OS) was investigated. Results: We included 117 unselected, consecutive mCRC patients aged =70 years undergoing systemic therapy for mCRC between February 2009 and July 2022. Median OS was 25.6 months (95% CI: 21.8-29.4). The median age was 78 years (range: 70-90) and 21%, 48%, 26% and 5% had an ECOG performance score of 0, 1, 2, and 3, respectively. The median number of systemic therapy lines was 2 (range: 1-5). The choice of first-line chemotherapy backbone (doublet/triplet versus mono) did not impact OS (HR: 0.83, p=0.50) or the probability of receiving subsequent therapy (p=0.697). Metastasectomy and/or local ablative treatment in the liver, lung, peritoneumand/or other organswere applied in 26 patients (22%) with curative intent. First-line anti-EGFR-based therapy showed a trend towards longer OS compared to anti-VEGF-based therapy or chemotherapy alone in leftsided mCRC (anti-EGFR: 39.3 months versus anti-VEGF: 27.3 months versus chemotherapy alone: 13.8 months, p=0.105). In multivariable analysis, metastasectomy and/or local ablative treatment with curative intent (yes versus no, HR: 0.22, p<0.001), the ECOG performance score (2 versus 0, HR: 3.07, p=0.007; 3 versus 0, HR: 3.66, p=0.053) and the presence of liver metastases (yes versus no, HR: 1.79, p=0.049) were independently associated with OS. Conclusions: Our findings corroborate front-line monochemotherapy in combination with targeted therapy as the treatment of choice for elderly mCRC patients with palliative treatment intent. Metastasectomy and/or local ablative treatment with curative intent are feasible and may improve OS in selected elderly mCRC patients. [ABSTRACT FROM AUTHOR]

Purpose: Local ablative treatment (LAT) is increasingly combined with systemic therapy in oligometastatic breast cancer (OMBC), without a high-level evidence to support this strategy. We evaluated the addition of LAT to systemic treatment in terms of progression-free survival (PFS) and overall survival (OS). Secondary endpoints were local control (LC) and toxicity. We sought to identify prognostic factors associated with longer OS and PFS. Methods and materials: We identified consecutive patients treated between 2014 and 2018 for synchronous or metachronous OMBC (defined as ≤ 5 metastases). LAT included stereotactic body radiation therapy (SBRT) and volumetric modulated arc therapy (VMAT), surgery, cryotherapy and percutaneous radiofrequency ablation (PRA). PFS and OS were calculated, and Cox regression models analyzed for potential predictors of survival. Results: One hundred two patients were included (no-LAT, n = 62; LAT, n = 40). Sixty-four metastases received LAT. Median follow-up was 50.4 months (95% CI [44.4; 53.4]). One patient experienced grade 3 toxicity in the LAT group. Five-year PFS and OS were 34.75% (95% CI [24.42–45.26]) and 63.21% (95% CI [50.69–73.37]) respectively. Patients receiving both LAT and systemic therapy had longer PFS and OS than those with no-LAT ([HR 0.39, p = 0.002]) and ([HR 0.31, p = 0.01]). The use of LAT, HER2-positive status and hormone-receptor positivity were associated with longer PFS and OS whereas liver metastases led to worse PFS. Conclusions: LAT was associated with improved outcomes in OMBC when added to systemic treatment, without significantly increasing toxicity. The prognostic factors identified to extend PFS and OS may help guide clinicians in selecting patients for LAT.

BackgroundAge-standardized mortality rates for metastatic colorectal cancer (mCRC) are highest among elderly patients. In current clinical guidelines, treatment recommendations for this patient population are based on a limited number of clinical trials.Patients and methodsIn this monocentric, retrospective analysis we characterized patients aged ≥70 years undergoing systemic therapy for mCRC and overall survival (OS) was investigated.ResultsWe included 117 unselected, consecutive mCRC patients aged ≥70 years undergoing systemic therapy for mCRC between February 2009 and July 2022. Median OS was 25.6 months (95% CI: 21.8-29.4). The median age was 78 years (range: 70-90) and 21%, 48%, 26% and 5% had an ECOG performance score of 0, 1, 2, and 3, respectively. The median number of systemic therapy lines was 2 (range: 1-5). The choice of first-line chemotherapy backbone (doublet/triplet versus mono) did not impact OS (HR: 0.83, p=0.50) or the probability of receiving subsequent therapy (p=0.697). Metastasectomy and/or local ablative treatment in the liver, lung, peritoneum and/or other organs were applied in 26 patients (22%) with curative intent. First-line anti-EGFR-based therapy showed a trend towards longer OS compared to anti-VEGF-based therapy or chemotherapy alone in left-sided mCRC (anti-EGFR: 39.3 months versus anti-VEGF: 27.3 months versus chemotherapy alone: 13.8 months, p=0.105). In multivariable analysis, metastasectomy and/or local ablative treatment with curative intent (yes versus no, HR: 0.22, p

Background: We aimed to explore the role of local ablative treatment (LAT) in metastatic esophageal squamous cell cancer (ESCC) patients who received chemotherapy and identify patients who will most likely benefit. Methods: We analyzed data of metastatic ESCC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. The chi-square test was used to evaluate the unadjusted clinicopathological categorical variables between the two groups. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors of overall survival. Propensity score matching (PSM) was used to adjust the differences between the two groups. Results: Overall, 720 metastatic ESCC patients treated with chemotherapy were analyzed in this study; 63.2% of patients (n = 455) received LAT, including radiotherapy (n = 444), primary site surgery (n = 12), or lymph node dissection (n = 27). Gender (HR = 1.220, 95% CI: 1.024–1.453, p = 0.026), bone metastases (HR = 1.559, 95% CI: 1.292–1.882, p < 0.001), and liver metastases (HR = 1.457, 95% CI: 1.237–1.716, p < 0.001) were independent prognostic factors in the entire population. However, LAT was not an independent prognostic factor. Further subgroup analyses showed that LAT improved OS from 8.0 months to 10.0 months in patients with metastases other than bone/liver (HR = 0.759, 95% CI: 0.600–0.961, p = 0.022). LAT was not a prognostic factor in patients with bone/liver metastases (HR = 0.995, 95% CI: 0.799–1.239, p = 0.961). After PSM, the median OS was 8.0 months (95% CI: 7.2–8.8 months) and patients who received LAT had a better OS than patients without LAT (HR = 0.796, 95% CI: 0.653–0.968, p = 0.023). Patients with metastases other than bone/liver could benefit from LAT compared with those with bone/liver metastases. Conclusions: Our study indicated that metastatic ESCC patients with metastases other than bone/liver could derive additional benefit from LAT with systemic chemotherapy. [ABSTRACT FROM AUTHOR]

BackgroundWe aimed to explore the role of local ablative treatment (LAT) in metastatic esophageal squamous cell cancer (ESCC) patients who received chemotherapy and identify patients who will most likely benefit.MethodsWe analyzed data of metastatic ESCC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. The chi-square test was used to evaluate the unadjusted clinicopathological categorical variables between the two groups. Univariate and multivariate Cox regression analyses were conducted to identify independent prognostic factors of overall survival. Propensity score matching (PSM) was used to adjust the differences between the two groups.ResultsOverall, 720 metastatic ESCC patients treated with chemotherapy were analyzed in this study; 63.2% of patients (n = 455) received LAT, including radiotherapy (n = 444), primary site surgery (n = 12), or lymph node dissection (n = 27). Gender (HR = 1.220, 95% CI: 1.024–1.453, p = 0.026), bone metastases (HR = 1.559, 95% CI: 1.292–1.882, p < 0.001), and liver metastases (HR = 1.457, 95% CI: 1.237–1.716, p < 0.001) were independent prognostic factors in the entire population. However, LAT was not an independent prognostic factor. Further subgroup analyses showed that LAT improved OS from 8.0 months to 10.0 months in patients with metastases other than bone/liver (HR = 0.759, 95% CI: 0.600–0.961, p = 0.022). LAT was not a prognostic factor in patients with bone/liver metastases (HR = 0.995, 95% CI: 0.799–1.239, p = 0.961). After PSM, the median OS was 8.0 months (95% CI: 7.2–8.8 months) and patients who received LAT had a better OS than patients without LAT (HR = 0.796, 95% CI: 0.653–0.968, p = 0.023). Patients with metastases other than bone/liver could benefit from LAT compared with those with bone/liver metastases.ConclusionsOur study indicated that metastatic ESCC patients with metastases other than bone/liver could derive additional benefit from LAT with systemic chemotherapy.

The overall survival rate of patients with hepatocellular carcinoma (HCC) is still poor, and development of innovative therapy modalities is of crucial importance. We aimed to evaluate the efficacy of available treatment modalities and investigate their impact on survival. Patients with HCC were included to the study. Disease stages were determined according to the most commonly used classification systems. Treatment modalities for patients were determined as local ablative, local palliative, surgery, systemic cytotoxic treatment, tyrosine kinase inhibitors, and best supportive care (BSC).Among 100 patients, 81 were men and 19 were women, the median age was 64. According to the Barcelona Clinic Liver Cancer staging system (BCLC), 1% of the patients were at very early stage, 16.3% early-stage, 22.4% intermediate-stage, 56.1% advanced-stage, and 4.1% was at the terminal-stage. We observed significant difference with regards to overall survival (OS) rates among different disease stage (p< 0.001). Portal vein tumor thrombosis (PVTT) was reported in 42 patients, and the OS rate of patients with PVTT was poor (p= 0.001). Among the first-line treatments, 9 patients received local ablative therapy, 25 local palliative, 27 systemic cytotoxic, 12 tyrosine kinase inhibitors, 10 surgical resection, and 4 BSC. The difference with regards to OS ratios of treatment groups was significant (p< 0.0001). We observed differential impact of diverse treatment modalities on survival of HCC patients. The study also revealed importance of various factors such as tumor size, disease stage, serum alpha-fetoprotein level, hepatic function status, and tumor vascular invasion status on clinical outcome. [ABSTRACT FROM AUTHOR]

Purpose: Needle track seeding in the local treatment of hepatocellular carcinoma (HCC) is not yet evaluated for catheter-based high-dose-rate brachytherapy (HDR-BT), a novel local ablative technique. Material and methods: We report a retrospective analysis of 100 patients treated on 233 HCC lesions by HDR-BT (using 588 catheters in total). No needle or catheter track irradiation was used. Minimum required follow-up with imaging was 6 months. In case of suspected needle track seeding (intra- and/or extrahepatic) in follow-up, image fusion of follow-up CT/MRI with 3D irradiation plan was used to verify the location of a new tumor deposit within the path of a brachytherapy catheter at the time of treatment. Results: We identified 9 needle track metastases, corresponding to a catheter-based risk of 1.5% for any location of occurrence. A total of 7 metastases were located within the liver (catheter-based risk, 1.2%), and 2 metastases were located extrahepatic (catheter-based risk, 0.3%). Eight out of 9 needle track metastases were successfully treated by further HDR-BT. Conclusions: The risk for needle track seeding after interstitial HDR-BT of HCC is comparable to previous reports of percutaneous biopsies and radiofrequency ablation (RFA), especially in case of extrahepatic needle track metastases. To compensate for the risk of seeding, a track irradiation technique similar to track ablation in RFA should be implemented in clinical routine. [ABSTRACT FROM AUTHOR]

Background: Age-standardized mortality rates for metastatic colorectal cancer (mCRC) are highest among elderly patients. In current clinical guidelines, treatment recommendations for this patient population are based on a limited number of clinical trials., Patients and Methods: In this monocentric, retrospective analysis we characterized patients aged ≥70 years undergoing systemic therapy for mCRC and overall survival (OS) was investigated., Results: We included 117 unselected, consecutive mCRC patients aged ≥70 years undergoing systemic therapy for mCRC between February 2009 and July 2022. Median OS was 25.6 months (95% CI: 21.8-29.4). The median age was 78 years (range: 70-90) and 21%, 48%, 26% and 5% had an ECOG performance score of 0, 1, 2, and 3, respectively. The median number of systemic therapy lines was 2 (range: 1-5). The choice of first-line chemotherapy backbone (doublet/triplet versus mono) did not impact OS (HR: 0.83, p=0.50) or the probability of receiving subsequent therapy (p=0.697). Metastasectomy and/or local ablative treatment in the liver, lung, peritoneum and/or other organs were applied in 26 patients (22%) with curative intent. First-line anti-EGFR-based therapy showed a trend towards longer OS compared to anti-VEGF-based therapy or chemotherapy alone in left-sided mCRC (anti-EGFR: 39.3 months versus anti-VEGF: 27.3 months versus chemotherapy alone: 13.8 months, p=0.105). In multivariable analysis, metastasectomy and/or local ablative treatment with curative intent (yes versus no, HR: 0.22, p<0.001), the ECOG performance score (2 versus 0, HR: 3.07, p=0.007; 3 versus 0, HR: 3.66, p=0.053) and the presence of liver metastases (yes versus no, HR: 1.79, p=0.049) were independently associated with OS., Conclusions: Our findings corroborate front-line monochemotherapy in combination with targeted therapy as the treatment of choice for elderly mCRC patients with palliative treatment intent. Metastasectomy and/or local ablative treatment with curative intent are feasible and may improve OS in selected elderly mCRC patients., Competing Interests: FH received honoraria from Eli Lilly, Pierre Fabre, Amgen, Servier, Daiichi Sankyo, Merck, Sanofi and BMS; travel support from Servier, BMS, Roche, Merck, PharmaMar, Pfizer, Daiichi Sankyo, Sanofi and Pierre Fabre. GR received honoraria from Roche, Seagen, Daiichi Sankyo, Pfizer, Eli Lilly, Gilead, Novartis and Amgen; reports travel support from Amgen, Daiichi Sankyo, Eli Lilly, Gilead, Merck, Pfizer and Roche; reports a consulting or advisory role for Roche, AstraZeneca, Daiichi Sankyo, Gilead, Pfizer, Pierre Fabre, Eli Lilly, MSD, Novartis, Amgen and Merck. KS received honoraria and travel support from Servier, Amgen and Pfizer. Ronald Heregger received travel support from PharmaMar. DN received honoraria for advisory function from Boehringer Ingelheim Pharma GmbH & Co and Eli Lilly. MD received honoraria from Terumo Europe N.V. FR received travel grants and lecture honoraria from Intraop Medical and PharmaMar. RG reports a consulting or advisory role for Celgene, Novartis, Roche, BMS, Takeda, Abbvie, AstraZeneca, Janssen, MSD, Merck, Gilead, Daiichi Sankyo and Sanofi; honoraria from Celgene, Novartis, Amgen, Roche, BMS, Takeda, Abbvie, AstraZeneca, MSD, Merck, Sandoz, Gilead, Daiichi Sankyo, Sanofi; travel support from Celgene, Novartis, Roche, Amgen, BMS, Abbvie, AstraZeneca, Janssen, MSD, Gilead and Daiichi Sankyo; research funding from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, Abbvie, Gilead, Daiichi Sankyo. LW received honoraria from Amgen, Astellas, BMS, Daiichi Sankyo, GSK, Lilly, Merck, MSD, Novocure, PharmaMar, Pierre Fabre, Roche, Servier; consulting fees from Merck and MSD; research support from Novocure, Roche and Servier. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huemer, Dunkl, Rinnerthaler, Schlick, Heregger, Emmanuel, Neureiter, Klieser, Deutschmann, Roeder, Greil and Weiss.)

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Photodynamic therapy (PDT) is a well-investigated locoregional cancer treatment in which a systemically administered photosensitizer is activated locally by illuminating the diseased tissue with light of a suitable wavelength. PDT offers various treatment strategies in oncology, especially palliative ones. This article focuses on the development and evaluation of interstitial PDT for the treatment of solid tumors, particularly liver tumors. The PDT is mostly used for superficial and endoluminal lesions like skin or bladder malignancies and also more frequently applied for the treatment of lung, esophageal, and head and neck cancer. With the help of specially designed application systems, PDT is now becoming a practicable option for solid lesions, including those in parenchymal organs such as the liver. After intravenous treatment with the photosensitizer followed by interstitial light activation, contrast-enhanced computed tomography shows the development of therapy-induced necrosis around the light-guiding device. With the use of multiple devices, ablation of liver tumors seems to be possible, and no severe side effects or toxicities related to the treatment are reported. PDT can become a clinically relevant adjunct in the locoregional therapy strategies. [ABSTRACT FROM AUTHOR]