A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). @*Materials and Methods@#Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. @*Results@#RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). @*Conclusion@#GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP / Journal of the Korean Cancer Association, 대한암학회지

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP

In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers / Journal of the Korean Cancer Association, 대한암학회지

Plasma circulating tumor DNA (ctDNA) sequencing has demonstrated clinical utility for tumor molecular profiling at initial diagnosis or tumor progression in advanced solid cancers and is being rapidly incorporated into the clinical practice guidelines, including non–small cell lung and breast cancer. Despite relatively low sensitivity, plasma ctDNA sequencing has several advantages over tissue-based assays, including ease of sampling, rapid turnaround time, repeatability, and the ability to overcome spatial heterogeneity, which makes it ideal for investigating acquired resistance and monitoring tumor evolution and dynamics. With technological advancement and declining costs, the clinical application of plasma ctDNA is expanding, and numerous ongoing clinical trials are examining its potential to guide the management of advanced, localized, and even preclinical cancers of various tumor types. The ability of plasma ctDNA analysis to detect minimal residual disease following curative treatment in the absence of clinical disease is among its most promising attributes. Plasma ctDNA sequencing can also facilitate the conduct of clinical trials and drug development, particularly in immunotherapy. In order to incorporate plasma ctDNA sequencing for clinical decision-making, it is important to understand the preanalytical and analytical factors that may affect its sensitivity and reliability.

Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group / Journal of the Korean Cancer Association, 대한암학회지

Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

Post-bevacizumab Clinical Outcomes and the Impact of Early Discontinuation of Bevacizumab in Patients with Recurrent Malignant Glioma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Bevacizumab±irinotecan is effective for treatment of recurrent malignant gliomas. However, the optimal duration of treatment has not been established. MATERIALS AND METHODS: Ninety-four consecutive patients with recurrent malignant glioma who were treated with bevacizumab at our institutions were identified. Patients who continued bevacizumab until tumor progression were enrolled in a late discontinuation (LD) group, while those who stopped bevacizumab before tumor progression were enrolled in an early discontinuation (ED) group. Landmark analyses were performed at weeks 9, 18, and 26 for comparison of patient survival between the two groups. RESULTS: Among 89 assessable patients, 62 (69.7%) and 27 (30.3%) patients were categorized as the LD and ED groups, respectively. According to landmark analysis, survival times from weeks 9, 18, and 26 were not significantly different between the two groups in the overall population. However, the LD group showed a trend toward increased survival compared to the ED group among responders. In the ED group, the median time from discontinuation to disease progression was 11.4 weeks, and none of the patients showed a definite rebound phenomenon. Similar median survival times after disease progression were observed between groups (14.4 weeks vs. 15.7 weeks, p=0.251). Of 83 patients, 38 (45.8%) received further therapy at progression, and those who received further therapy showed longer survival in both the LD and ED groups. CONCLUSION: In recurrent malignant glioma, duration of bevacizumab was not associated with survival time in the overall population. However, ED of bevacizumab in responding patients might be associated with decreased survival.

Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. MATERIALS AND METHODS: Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. RESULTS: Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, -42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. CONCLUSION: Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.

Two cases of thyroid small cell carcinoma / 대한내과학회지

Historically, small cell carcinoma in the thyroid has been regarded as a kind of lymphoma and small cell carcinoma in the thyroid as a distinct disease entity is still controversial. Here, we present two cases of thyroid small cell carcinoma that were differentiated from lymphoma, based on immunohistochemical staining. One case was misdiagnosed as anaplastic carcinoma that occurred during the treatment of follicular carcinoma. Both cases responded well to chemotherapy. These cases support the hypothesis that thyroid small cell carcinoma is a distinct disease entity. One should consider small cell carcinoma when there is a rapidly growing mass in the thyroid.

Sunitinib-induced reversible posterior leukoencephalopathy syndrome after rifampin discontinuation / 대한내과학회지

Sunitinib is an oral tyrosine kinase inhibitor with anti-angiogenic activity that is used for the treatment of advanced renal cell carcinoma and advanced gastrointestinal stromal tumors after failure on imatinib. The most common adverse effects of sunitinib are fatigue, diarrhea, nausea, stomatitis, hypertension, hand-foot syndrome, and cytopenia. Sunitinib was recently reported to be associatedwith reversible posterior leukoencephalopathy syndrome (RPLS). Here, we report the case of a 76-year-old woman with sunitinib- induced RPLS that developed after rifampin discontinuation.

Sunitinib-induced reversible posterior leukoencephalopathy syndrome after rifampin discontinuation / 대한내과학회지

Sunitinib is an oral tyrosine kinase inhibitor with anti-angiogenic activity that is used for the treatment of advanced renal cell carcinoma and advanced gastrointestinal stromal tumors after failure on imatinib. The most common adverse effects of sunitinib are fatigue, diarrhea, nausea, stomatitis, hypertension, hand-foot syndrome, and cytopenia. Sunitinib was recently reported to be associatedwith reversible posterior leukoencephalopathy syndrome (RPLS). Here, we report the case of a 76-year-old woman with sunitinib- induced RPLS that developed after rifampin discontinuation.

Discovery of an inta-atrial extension of hepatocellular carcinoma in a patient presenting with right-heart failure / 대한내과학회지

A primary right atrial (RA) mass is not common; instead, most tumors in the right atrium originate from metastasis through the caval route. Here we describe a patient with a huge RA tumor that showed contiguous spread from the inferior vena cava. This 60-year-old patient, positive for hepatitis B surface antigen, visited the emergency department of our institution due to recently aggravated dyspnea. Transthoracic and transesophageal echocardiography clearly demonstrated a huge RA mass, 6.5x6.0 cm, causing flow disturbance. Cardiac magnetic resonance imaging and dynamic computed tomography of the liver showed multiple large hepatic masses that extended into the right atrium, with tumor thrombi in the inferior vena cava. Given the enhancement pattern in dynamic computed tomography of the liver, the hepatic mass was diagnosed as hepatocellular carcinoma. Due to the risk of spontaneous rupture of the mass, emergency transarterial chemoembolization was performed, without complications. Thereafter, thalidomide, which has been shown to have anti-angiogenic effects, was prescribed to the patient.