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.

Late Recurrence in a Rectal Cancer Patient Who Underwent Preoperative Chemoradiotherapy Followed by Local Excision: A Case Report

Some patients who have undergone preoperative chemoradiotherapy (CRT) following surgery have been diagnosed with late recurrence more than 5 years after treatment, raising questions about the possible benefit extending surveillance beyond the recommended 5 years. In 2011, a 71-year-old male patient was diagnosed with T3N+ low-lying rectal cancer located 3 cm from the anal verge before undergoing long-course preoperative CRT. After CRT, the patient was reexamined and diagnosed with ycT1–2N0 lesion, so local excision (LE) was performed. The patient underwent intensive surveillance for up to 5 years, and no evidence of recurrence was found. At 74 months after surgery, the patient was hospitalized for a hematochezia, and local recurrence at the excision site and peritoneal seeding nodules were identified. Considering the late recurrence in this patient, it might be necessary to long-term follow-up beyond 5 years in patients with preoperative CRT followed by LE.

Late Recurrence in a Rectal Cancer Patient Who Underwent Preoperative Chemoradiotherapy Followed by Local Excision: A Case Report

Some patients who have undergone preoperative chemoradiotherapy (CRT) following surgery have been diagnosed with late recurrence more than 5 years after treatment, raising questions about the possible benefit extending surveillance beyond the recommended 5 years. In 2011, a 71-year-old male patient was diagnosed with T3N+ low-lying rectal cancer located 3 cm from the anal verge before undergoing long-course preoperative CRT. After CRT, the patient was reexamined and diagnosed with ycT1–2N0 lesion, so local excision (LE) was performed. The patient underwent intensive surveillance for up to 5 years, and no evidence of recurrence was found. At 74 months after surgery, the patient was hospitalized for a hematochezia, and local recurrence at the excision site and peritoneal seeding nodules were identified. Considering the late recurrence in this patient, it might be necessary to long-term follow-up beyond 5 years in patients with preoperative CRT followed by LE.

Identification of a Novel Splice Variant (c.423-8A>G) of APC by RNA Sequencing

No abstract available.

A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair–Deficient/Microsatellite Instability–High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations. @*Materials and Methods@#In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1. @*Results@#The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in 4 and 2 patients, respectively, with no treatment-related deaths. @*Conclusion@#Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.

Hepatic resection after neoadjuvant chemotherapy for patients with liver metastases from colorectal cancer: need for cautious planning

PURPOSE: Current neoadjuvant chemotherapy (NAC) may enable therapies such as surgical resection and local ablation of metastases in patients with colorectal liver metastasis (CLM). We evaluated outcomes in CLM patients who underwent resection and/or local treatment after NAC and identified prognostic factors for oncologic outcomes. METHODS: Patients who received NAC followed by resection and/or local treatment of hepatic metastasis from 2013 to 2015 were included. Treatment and tumor-related variables were tabulated. Recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox regression analysis was used to identify factors associated with RFS and OS. RESULTS: Sixty-eight patients received NAC followed by resection and/or local treatment of hepatic metastases. Targeted therapy was administered in 50% of the patients. RFS was 35.8% at 1 year and 19.4% at 2 years postoperatively. OS was 95.6% at 1 year and 88.2% at 2 years postoperatively. In the multivariable analysis, R1 resection margin (hazard ratio [HR], 3.95; P = 0.008) of the liver metastases and ypN1/ypN2 (HR, 2.356 and 1.983, respectively; P = 0.041) were associated with poor RFS. Both factors were also significantly related to OS. CONCLUSION: Resection margin of the metastatic tumor and ypN status are the only relevant factors for RFS and OS in CLM patients treated with NAC. Despite early and high rates of recurrence, CLM patients treated with NAC who undergo resection and/or local treatment have acceptable OS. Multidisciplinary review of candidates for surgery and cautious planning are crucial for achieving optimal outcomes.

Prospective Validation of The Korean Cancer Study Group Geriatric Score (KG)-7, a Novel Geriatric Screening Tool, in Older Patients with Advanced Cancer Undergoing First-line Palliative Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy. MATERIALS AND METHODS: Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC). RESULTS: The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006). CONCLUSION: KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.

Unusual Local Recurrence with Distant Metastasis after Successful Endoscopic Submucosal Dissection for Colorectal Mucosal Cancer

Intramucosal colorectal cancer (CRC) is thought not to metastasize because the colonic lamina propria lacks lymphatics. Only a few recent case reports have suggested lymph node metastasis from intramucosal CRC, but there is no clear evidence supporting the metastatic potential of intramucosal CRC. Hence, endoscopic resection is regarded as curative treatment for intramucosal CRC. This report describes two cases of unusual local recurrence with distant metastasis in patients who had previously undergone successful endoscopic submucosal dissection for intramucosal CRC. The recurrent colorectal lesions developed at the site of the previous endoscopic submucosal dissection scars in a relatively short-term period, and the pathologic findings showed an “undermining” invasion pattern without surrounding mucosal change. Based on the clinical course and pathological findings, we concluded that the second colorectal lesions were recurrences rather than de novo cancers.

Use of a High-Throughput Genotyping Platform (OncoMap) for RAS Mutational Analysis to Predict Cetuximab Efficacy in Patients with Metastatic Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Cetuximab demonstrates improved efficacy outcomes in patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS exon 2. Resistance to cetuximab is mediated by activating less frequent mutations in the RAS genes beyond KRAS exon 2. We performed extended RAS Mutational analysis using a high-throughput genotyping platform (OncoMap) and evaluated extended RAS analysis for predicting cetuximab efficacy in patients harboring wild-type KRAS exon 2 tumors following Sanger sequencing. MATERIALS AND METHODS: Extended RAS analysis was performed on 227 wild-type KRAS exon 2 mCRC patients who received cetuximab as salvage treatment using OncoMap ver. 4.0. Targeted genes included exon 2, exon 3, and exon 4, both in KRAS and NRAS, and included BRAF exon 15. We assessed efficacy by the new RAS mutation status. RESULTS: The OncoMap detected 57 additional mutations (25.1%): 25 (11%) in KRAS exon 2 and 32 (14.1%) beyond KRAS exon 2. Survival differences were observed after dividing patients into the wild-type RAS group (n=170) and mutant RAS group (n=57) using OncoMap. Progression-free survival was 4.8 months versus 1.8 months (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.32 to 0.61), and overall survival was 11.9 months versus 8.4 months (HR, 0.65; 95% CI, 0.47 to 0.88). CONCLUSION: Sanger sequencing is not sufficient for selecting candidates for cetuximab treatment. High-throughput extended RAS genotyping is a feasible approach for this purpose and identifies patients who might benefit from cetuximab treatment.

Paired Primary and Metastatic Tumor Analysis of Somatic Mutations in Synchronous and Metachronous Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although the mutation status of KRAS is highly concordant in primary and metastatic lesions, it has not been generalized to other major pathway genes. MATERIALS AND METHODS: In this study, 41 genes were evaluated and the mutational profiles were compared in 46 colorectal cancer patients with paired surgical specimens of primary and metastatic lesions: synchronous (n=27) and metachronous (n=19) lesions. A high-throughput mass spectrometry-based genotyping platform validated by orthogonal chemistry, OncoMap v.4.4, was used to evaluate the formalin-fixed, paraffin-embedded surgical specimens. The patients’ demographics, tumor characteristics, and microsatellite instability status were analyzed by a retrospective chart review. RESULTS: In this study,with OncoMap, mutationswere identified in 80.4% of patientswith the following frequency: KRAS (39.1%), TP53 (28.3%), APC (28.3%), PIK3CA (6.5%), BRAF (6.5%), and NRAS (4.3%). Although 19.6% (9/46) of the patients showed no gene mutations, 43.5% (20/46) and 37.0% (17/46) had mutations in one and two or more genes, respectively. The synchronous and metachronous lesions showed similar mutational profiles. Paired samples between primary and metastatic tumors differed in 7.4% (2/27) and 10.5% (2/19) for synchronous and metachronous according to OncoMap. CONCLUSION: These findings indicate the major pathway genes, including KRAS, TP53, APC, PIK3CA, BRAF, and NRAS, are often concordant between the primary and metastatic lesions regardless of the temporal relationship of metastasis.

Inflammatory Myofibroblastic Tumor Showing Durable Remission after Anthracycline-Containing Cytotoxic Chemotherapy: Report of a Case / 대한내과학회지

An inflammatory myofibroblastic tumor (IMT) is a rare disease entity, and the clinical characteristics range from indolent to aggressive forms. No established management for patients with unresectable or aggressive IMT is available. We report on a 62-year-old patient with aggressive IMT who achieved a durable partial response lasting 12 months after anthracycline-containing cytotoxic chemotherapy without corticosteroids. The patient was admitted for an evaluation of progressive weight loss and lower abdominal pain lasting for 2 weeks. Abdominopelvic computed tomography revealed a 10 cm sized heterogeneous mass in the mesentery that encased the superior mesenteric artery and a liver metastasis. The diagnosis of IMT was confirmed by percutaneous core needle biopsy of the mesenteric mass. Systemic chemotherapy was performed after confirming disease progression during a 1 month observation period. A partial response was obtained after two cycles of chemotherapy. Anthracycline-containing cytotoxic chemotherapy could be a treatment option for patients with aggressive IMT.

Inflammatory Myofibroblastic Tumor Showing Durable Remission after Anthracycline-Containing Cytotoxic Chemotherapy: Report of a Case / 대한내과학회지

An inflammatory myofibroblastic tumor (IMT) is a rare disease entity, and the clinical characteristics range from indolent to aggressive forms. No established management for patients with unresectable or aggressive IMT is available. We report on a 62-year-old patient with aggressive IMT who achieved a durable partial response lasting 12 months after anthracycline-containing cytotoxic chemotherapy without corticosteroids. The patient was admitted for an evaluation of progressive weight loss and lower abdominal pain lasting for 2 weeks. Abdominopelvic computed tomography revealed a 10 cm sized heterogeneous mass in the mesentery that encased the superior mesenteric artery and a liver metastasis. The diagnosis of IMT was confirmed by percutaneous core needle biopsy of the mesenteric mass. Systemic chemotherapy was performed after confirming disease progression during a 1 month observation period. A partial response was obtained after two cycles of chemotherapy. Anthracycline-containing cytotoxic chemotherapy could be a treatment option for patients with aggressive IMT.

Quality of Life in Colorectal Cancer Patients with Chemotherapy-Induced Peripheral Neuropathy / 종양간호학회지

PURPOSE: The purpose of this study was to identify the quality of life in colorectal cancer patients with chemotherapy-induced peripheral neuropathy. METHODS: A total of 93 patients were recruited in the cross-sectional survey design. Quality of life in colorectal cancer patients were measured by European Organization for Research and Treatment of Cancer (EORTC) QLQ C30 and CIPN20. RESULTS: In the QLQ C30, the mean score of the global health status was 59.41, the functional scale was 73.29 and symptom scale was 26.72. In CIPN20, the mean score of sensory scale was 32.70, autonomic scale was 22.88 and motor scale was 16.12. In the QLQ C30, the global health status showed significant differences according to surgery (p=.027) and the functional scale, and the symptom scale showed significant differences according to gender (p=.046, p=.020) and nonpharmacologic intervention (p=.001, p=.009). The CIPN20, the sensory scale showed significant differences according to age (p=.006), DM (p=.005), grade of CIPN (p=<.001) the status of chemotherapy (p=.001) and nonpharmacologic intervention (p=.010). CONCLUSION: The level of quality of life in colorectal cancer patients with peripheral neuropathy was relatively low. There is a need for developing a nursing intervention for colorectal cancer patients to improve their quality of life and to decrease chemotherapy-induced peripheral neuropathy.

Chemotherapy for Colorectal Cancer

Survival outcomes have been steadily improving for last 50 years in patients with colorectal cancer. The 5-fluorouracil (5-FU) is still one of the major chemotherapeutic agents. New cytotoxic agents, irinotecan and oxaliplatin, or targeted agents, bevacizumab and cetuximab, have been studied in the treatment of colon cancer. Adjuvant chemotherapy is indicated in patients with colon cancer at high-risk stage II and III, and after complete resection. Oxaliplatin-based regimens, FOLFOX, are considered as the standard adjuvant chemotherapy. If there are contraindications for oxaliplatin, the best alternatives are capecitabine or 5FU/LV. In rectal cancer, adjuvant chemotheradiotherapy is indicated in patients who had curative resection with stage II and III cancer. Adjuvant chemotherapy is necessary after neoadjuvant chemoradiotherapy in rectal cancer. The introduction of novel agents targeted to specific molecular features of cancer cells promises more options and marked improvements in efficacy for treatment of metastatic colon cancer. Bevacizumab has been shown to extend survival in colorectal cancer when used in combination with irinotecan and 5-fluorouracil-based chemotherapy, and the addition of cetuximab to irinotecan and 5-fluorouracil-based chemotherapy eliminates irinotecan resistance. Interestingly, there has been no clear association between the expression of epidermal growth factor receptor (EGFR) and response to the EGFR inhibitors. Instead, KRAS mutation has been accepted as a negative predictive factor for the treatment of cetuximab. In contrast, no valid biomarkers for bevacizimab were found so far. More studies are necessary to identify biomarkers of targeted agents. Recent advancement of chemotherapeutic agents extended survival in colorectal cancer.

Chemotherapy for Colorectal Cancer / 대한소화기학회지

Recent advances in chemotherapy lead to improved survival outcomes in patients with colorectal cancer. The 5-fluorouracil (5-FU) is still one of the important chemotherapeutic agents since 1950s, but the introduction of newer cytotoxic agents, irinotecan and oxaliplatin, or targeted agents, bevacizumab and cetuximab, have changed treatment strategies for these patients. A deliberate choice should be made for adjuvant chemotherapy, because it has became complicated more than ever before. Oxaliplatin plus 5-FU seemed to be superior in terms of disease-free and overall survival than 5-FU alone after curative surgery for colon cancers. However not all of these patients seemed to receive benefit from this intensive adjuvant treatment, and some limitations are present according to the postoperative stage, tumor biology and clinical characteristics. For metastatic disease, there is no doubt that more complicated strategies are present because we have more abundant chemotherapeutic agents available for metastatic setting compared to adjuvant setting. Recently, targeted agents, such as bevacizumab or cetuximab, also took an important place in the treatment of metastatic colorectal cancer, and many efforts are also made to find the biomarkers for predicting treatment responses to these targeted agents. In this review, we intended to sort up the standard strategies of chemotherapy for patients with colorectal cancer according to the latest pivotal publications.

Intracranial Relapse of Intravascular Large B-Cell Lymphoma After Completion of CHOP Chemotherapy / 대한혈액학회지

Intravascular large B-cell lymphoma (IVLBL) is a rare neoplasm characterized by proliferation of lymphoma cells within the lumina of small vessels. Neurological and skin involvements usually predominate. We would describe a 78-year-old woman presented with fever, multiple erythematous skin lesions, and language disturbance. The skin biopsy of breast revealed IVLBL and malignant cells were also seen in the bone marrow. Shortly after completion of six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) with clinical response, intracranial relapse with multiple brain masses occurred. The palliative whole brain radiation therapy was given and intensive chemotherapy should be investigated in the case presented here.

A Case of Coexistence of Malignant Lymphoma and Papillary Carcinoma in Thyroid / 대한혈액학회지

A 65 year-old female visited because of neck mass. Tumors were found in thyroid, neck nodes, lung parenchyma, liver, kidney and bone. Biopsy of neck node revealed malignant lymphoma (diffuse large B cell lineage) and metastatic papillary thyroid carcinoma simultaneously. Her thyroid function was normal. She was treated with chemotherapy targeting malignant lymphoma initially, and achieved near complete remission. Additional biopsy of neck node after first chemotherapy revealed no papillary carcinoma. To our knowledge, this is the first report of malignant lymphoma and papillary carcinoma simultaneously involving thyroid gland in Korea.

Partial Anomalous Pulmonary Venous Return into Coronary Sinus with Intact Atrial Septum

We report a case of partial anomalous pulmonary venous return where the right upper and lower pulmonary veins drain into the coronary sinus with right-to-left shunt via patent foramen ovale. To our knowledge, this is the uncommon case where the interatrial septum is intact. The diagnosis was initially made by transthoracic echocardiography and transesophageal echocardiography with the infusion of agitated saline and confirmed by pulmonary artery angiography. Curative operation could not be performed because of the irreversible pulmonary hypertension.