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Purpose@#For precision medicine, exploration and monitoring of molecular biomarkers are essential. However, in advanced gastric cancer (GC) with visceral lesions, an invasive procedure cannot be performed repeatedly for the follow-up of molecular biomarkers. @*Materials and Methods@#To verify the clinical implication of serial liquid biopsies targeting circulating tumor DNA (ctDNA) on treatment response, we conducted targeted deep sequencing for serially collected ctDNA of 15 HER2-positive metastatic GC patients treated with anti-PD-1 inhibitor in combination with standard systemic treatment. @*Results@#In the baseline ctDNAs, 14 patients (93%) harbored more than one genetic alteration. A number of mutations in wellknown cancer-related genes, such as KRAS and PIK3CA, were identified. Copy number alterations were identified in eight GCs (53.3%), and amplification of the ERBB2 gene (6/15, 40.0%) was the most recurrent. When we calculated the mean variant allele frequency (VAF) of mutations in each ctDNA as the molecular tumor burden index (mTBI), the mTBI trend was largely consistent with the VAF profiles in both responder and non-responder groups. Notably, in the longitudinal analysis of ctDNA, mTBI provided 2–42 weeks (mean 13.4 weeks) lead time in the detection of disease progression compared to conventional follow-up with CT imaging. @*Conclusion@#Our data indicate that the serial genetic alteration profiling of ctDNA is feasible to predict treatment response in HER2-positive GC patients in a minimally invasive manner. Practically, ctDNA profiles are useful not only for the molecular diagnosis of GC but also for the selection of GC patients with poor prognosis for systemic treatment (ClinicalTrials.gov identifier:NCT02901301).
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Purpose@#Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide.National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC. @*Materials and Methods@#We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the “before COVID” period, and the years 2020 and 2021 as the “during COVID” period. @*Results@#Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it.Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years. @*Conclusions@#During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.
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Purpose@#There are clinical unmet needs in predicting therapeutic response and precise strategy for the patient with advanced biliary tract cancer (BTC). We aimed to identify genomic alterations predicting therapeutic response and resistance to gemcitabine and cisplatin (Gem/Cis)-based chemotherapy in advanced BTC. @*Materials and Methods@#Genomic analysis of advanced BTC multi-institutional cohorts was performed using targeted panel sequencing. Genomic alterations were analyzed integrating patients’ clinicopathologic data, including clinical outcomes of Gem/Cis-based therapy. Significance of genetic alterations was validated using clinical next-generation sequencing (NGS) cohorts from public repositories and drug sensitivity data from cancer cell lines. @*Results@#193 BTC patients from three cancer centers were analyzed. Most frequent genomic alterations were TP53 (55.5%), KRAS (22.8%), ARID1A (10.4%) alterations, and ERBB2 amplification (9.8%). Among 177 patients with BTC receiving Gem/Cis-based chemotherapy, ARID1A alteration was the only independent predictive molecular marker of primary resistance showing disease progression for 1st-line chemotherapy in the multivariate regression model (odds ratio, 3.12; p=0.046). In addition, ARID1A alteration was significantly correlated with inferior progression-free survival on Gem/Cis-based chemotherapy in the overall patient population (p=0.033) and in patients with extrahepatic cholangiocarcinoma (CCA) (p=0.041). External validation using public repository NGS revealed that ARID1A mutation was a significant predictor for poor survival in BTC patients. Investigation of multi-OMICs drug sensitivity data from cancer cell lines revealed that cisplatin-resistance was exclusively observed in ARID1A mutant bile duct cancer cells. @*Conclusion@#Integrative analysis with genomic alterations and clinical outcomes of the first-line Gem/Cis-based chemotherapy in advanced BTC revealed that patients with ARID1Aalterations showed a significant worse clinical outcome, especially in extrahepatic CCA. Well-designed prospective studies are mandatory to validate the predictive role of ARID1Amutation.
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Purpose@#Neuregulin 1 (NRG1) gene fusion is a potentially actionable oncogenic driver. The oncoprotein binds to ERBB3-ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic approach for inhibiting ERBB3/ERBB2. However, the frequency and clinicopathological features of solid tumors harboring NRG1 fusions in Korean patients remain largely unknown. @*Materials and Methods@#We reviewed archival data from next-generation sequencing panel tests conducted at a single institution, specifically selecting patients with in-frame fusions that preserved the functional domain. The clinicopathological characteristics of patients harboring NRG1 fusions were retrospectively reviewed. @*Results@#Out of 8,148 patients, NRG1 fusions were identified in 22 patients (0.27%). The average age of the patients was 59 years (range, 32 to 78 years), and the male-to-female ratio was 1:1.2. The lung was the most frequently observed primary site (n=13), followed by the pancreaticobiliary tract (n=3), gastrointestinal tract (n=2, stomach and rectum each), ovary (n=2), breast (n=1), and soft tissue (n=1). Histologically, all tumors demonstrated adenocarcinoma histology, with the exception of one case of sarcoma. CD74 (n=8) and SLC3A2 (n=4) were the most frequently identified fusion partners. Dominant features included the presence of fewer than three co-occurring genetic alterations, a low tumor mutation burden, and low programmed death-ligand 1 expression. Various clinical responses were observed in patients with NRG1 fusions. @*Conclusion@#Despite the rarity of NRG1 fusions in Korean patients with solid tumors, identification through next-generation sequencing enables the possibility of new targeted therapies.
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Purpose@#We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). @*Materials and Methods@#Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. @*Results@#Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. @*Conclusion@#CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.
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Purpose@#Melanoma is a potentially fatal cutaneous malignancy and regional lymph node (LN) metastases are the most important predictors of mortality. This study aimed to analyze clinical features and risk factors of complications associated with inguinal LN dissection (LND) to establish treatment protocols. @*Methods@#This single-center retrospective study (2000 to 2018) consisted of patients who underwent inguinal area sentinel LN biopsy (SLNB) or LND due to malignant melanoma. Risk factors and outcomes were analyzed. @*Results@#One hundred patients underwent SLNB alone (n=67; patients with negative SLNB), complete LND (CLND) after positive SLNB (n=19), or radical LND without SLNB (n=14). Five-year overall survival and disease-free survival rates among these groups were 87.3%, 57.4%, and 61.9%, and 59.0%, 22.7%, and 28.1%, respectively. The complication rate in the SLNB alone group was lower than the other groups (22.4% vs. 47.4% and 35.7%, respectively; P=0.048). Seroma was the most common complication in the SLNB alone group (15.0%); lymphedema was most common in the CLND after SLNB group (21.1%). Multivariate analysis of risk factors for postoperative complications found the hazard ratio for body mass index >28 kg/m2 was 4.376 (95% confidence interval [CI], 1.243–15.401; P=0.022). The hazard ratio for LND (including CLND after SLNB and radical LND without SLNB) was 3.263 (95% CI, 1.248–8.529; P=0.016). @*Conclusion@#Inguinal LND is a higher risk procedure compared to SLNB and other sites for postoperative complications, irrespective of meticulous surgical techniques. More studies are needed to establish treatment protocols (e.g., observation vs. CLND after a positive SLNB result) and the risks and benefits in Asian populations.
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Purpose@#We investigated the clinical efficacy of immune checkpoint blocker (ICB) therapy for metastatic or advanced melanoma in Korean patients. As well, we assessed whether the effects of ICBs can be enhanced by combination therapy with palliative radiotherapy (RT). @*Materials and Methods@#We retrospectively reviewed the records of 127 patients with metastatic melanoma who received ICB with or without palliative RT between 2014 and 2018. The melanoma subtypes were classified as follows: chronic sun-damaged (CSD), acral, mucosal, and uveal. The primary endpoint was the objective response rate (ORR). @*Results@#The overall ORR was 15%, with 11 complete and eight partial responses. ORRs for CSD, acral/mucosal, and uveal melanomas were 50%, 16.5%, and 0%, respectively (p=0.009). In addition to the subtype, stage at treatment, total tumor burden at treatment, and ICB type were significantly associated with ORR (all p < 0.05). Palliative RT was administered in 44% of patients during the treatment, and it did not affect ORR. Clinical responders to ICB therapy exhibited significantly higher 1-year progression-free and overall survival rates than nonresponders. @*Conclusion@#ORR for ICB monotherapy in Korean patients with melanoma is relatively modest compared with that in Western patients because the non-CSD subtypes are predominant in the Korean population. Our findings regarding combination therapy with ICB provided a rationale for the initiation of our phase II study (NCT04017897).
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Purpose@#Melanoma is a potentially fatal cutaneous malignancy and regional lymph node (LN) metastases are the most important predictors of mortality. This study aimed to analyze clinical features and risk factors of complications associated with inguinal LN dissection (LND) to establish treatment protocols. @*Methods@#This single-center retrospective study (2000 to 2018) consisted of patients who underwent inguinal area sentinel LN biopsy (SLNB) or LND due to malignant melanoma. Risk factors and outcomes were analyzed. @*Results@#One hundred patients underwent SLNB alone (n=67; patients with negative SLNB), complete LND (CLND) after positive SLNB (n=19), or radical LND without SLNB (n=14). Five-year overall survival and disease-free survival rates among these groups were 87.3%, 57.4%, and 61.9%, and 59.0%, 22.7%, and 28.1%, respectively. The complication rate in the SLNB alone group was lower than the other groups (22.4% vs. 47.4% and 35.7%, respectively; P=0.048). Seroma was the most common complication in the SLNB alone group (15.0%); lymphedema was most common in the CLND after SLNB group (21.1%). Multivariate analysis of risk factors for postoperative complications found the hazard ratio for body mass index >28 kg/m2 was 4.376 (95% confidence interval [CI], 1.243–15.401; P=0.022). The hazard ratio for LND (including CLND after SLNB and radical LND without SLNB) was 3.263 (95% CI, 1.248–8.529; P=0.016). @*Conclusion@#Inguinal LND is a higher risk procedure compared to SLNB and other sites for postoperative complications, irrespective of meticulous surgical techniques. More studies are needed to establish treatment protocols (e.g., observation vs. CLND after a positive SLNB result) and the risks and benefits in Asian populations.
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PURPOSE: We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients. MATERIALS AND METHODS: Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2/day on days 1-14 plus docetaxel 35 mg/m2on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2/day on days 1-14 plus cisplatin 60 mg/m2on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate. RESULTS: Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment. CONCLUSION: Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.
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Humanos , Anemia , Capecitabina , Quimioterapia Adjuvante , Cisplatino , Intervalo Livre de Doença , Seguimentos , Gastrectomia , Síndrome Mão-Pé , Coreia (Geográfico) , Excisão de Linfonodo , Mucosite , Neutropenia , Neoplasias GástricasRESUMO
von Hippel-Lindau (VHL) disease is an autosomal dominant inherited tumor syndrome associated with mutations of the VHL tumor suppressor gene located on chromosome 3p25. The loss of functional VHL protein contributes to tumorigenesis. This condition is characterized by development of benign and malignant tumors in the central nervous system (CNS) and the internal organs, including kidney, adrenal gland, and pancreas. We herein describe the case of a 74-year-old man carrying the VHL gene mutation who was affected by simultaneous colorectal adenocarcinoma, renal clear cell carcinoma, and hemangioblastomas of CNS.
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Idoso , Humanos , Adenocarcinoma , Glândulas Suprarrenais , Carcinogênese , Carcinoma de Células Renais , Sistema Nervoso Central , Neoplasias Colorretais , Genes Supressores de Tumor , Hemangioblastoma , Rim , Pâncreas , Doença de von Hippel-LindauRESUMO
PURPOSE: There is no standard second-line regimen for malignant melanoma patients with disease progression after first-line chemotherapy, and platinum-alkylating agents combined with paclitaxel have shown modest efficacy. MATERIALS AND METHODS: We conducted a phase II, open-label, single-arm study to test the efficacy of docetaxel combined with carboplatin for malignant melanoma patients who failed previous treatment with dacarbazine. Intravenous docetaxel (35 mg/m2 on days 1 and 8 of each cycle) and carboplatin (area under the curve 3 on days 1 and 8 of each cycle) was administered every 21 days. Primary end point was objective response rate (ORR). RESULTS: Thirty patients were enrolled in the study, and the median follow-up duration was 19.8 months. Among 25 per-protocol patients, there were three responders (1 with complete response and 2 with partial response) and 17 stable disease patients (ORR, 12.0%). Among the per-protocol population, the median progression-free survival (PFS) was 4.3 months and the median overall survival (OS) was 9.6 months. Uveal melanoma patients (n=9) showed the best prognosis compared to other subtypes (median PFS, 7.6 months; OS, 9.9 months). The most common grade 3 or 4 adverse event was neutropenia (n=15, 50.0%). CONCLUSION: Docetaxel combined with carboplatin showed association with an acceptable safety profile and overall efficacy for patients with malignant melanoma who had progressed on chemotherapy containing dacarbazine.
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Humanos , Carboplatina , Dacarbazina , Progressão da Doença , Intervalo Livre de Doença , Tratamento Farmacológico , Seguimentos , Melanoma , Neutropenia , Paclitaxel , PrognósticoRESUMO
A 50-year-old woman with incidentally detected multiple gastric polyps and biopsy-proven neuroendocrine tumor (NET) was referred to our hospital. More than 10 polypoid lesions (less than 15 mm) with normal gastric mucosa were detected from the gastric body to the fundus. The serum level of gastrin was within the normal limits. There was no evidence of atrophic changes on endoscopy and serologic marker as pepsinogen I/II ratio. Computed tomography of the abdomen and pelvis revealed no evidence of metastatic lesions. She refused surgery, and we performed endoscopic polypectomy for almost all the gastric polyps that were greater than 5 mm. Although the histological examination revealed that all the removed polys were diagnosed as NET G1, three of them extended to the lateral or vertical resection margins, while two exhibited lymphovascular invasion. A follow-up upper endoscopy that was performed 6 months after the diagnosis showed multiple remnant gastric polyps that were suggestive of remnant gastric NET.
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Feminino , Humanos , Pessoa de Meia-Idade , Abdome , Diagnóstico , Endoscopia , Seguimentos , Mucosa Gástrica , Gastrinas , Tumores Neuroendócrinos , Pelve , Pepsinogênio A , Pólipos , EstômagoRESUMO
A 21-year-old woman with a history of systemic lupus erythematosus (SLE) was admitted with dyspnea on exertion for a year. A transesophageal echocardiogram showed dilated aortic root with intimal thickening. A positron emission tomography/computed tomography demonstrated increase in glucose hypermetabolic along the walls of the aortic valve, ascending aorta, aortic arch, and aorta, vasculitis was observed. She underwent the Bentall operation due to inflammation at sinus of right coronary cusp. She started high dose glucocorticoid after the operation. Currently she is able to sustain with low dose steroid after gradually tapered. Her symptoms were disappeared, and inflammatory markers decreased to within the normal range. Aortitis and aortic aneurysms are an uncommon manifestation of SLE. Furthermore, almost of lupus patients with medium and large vessel vasculitis are not biopsied or studied histologically. We present first case in Korea that was a 21-year-old woman who diagnosed with lupus aortitis by pathology after aortic valve replacement operation.
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Feminino , Humanos , Adulto Jovem , Aorta , Aorta Torácica , Aneurisma Aórtico , Valva Aórtica , Aortite , Dispneia , Elétrons , Glucose , Inflamação , Coreia (Geográfico) , Lúpus Eritematoso Sistêmico , Patologia , Valores de Referência , VasculiteRESUMO
Malakoplakia is an uncommon chronic granulomatous inflammatory disease which is associated with immunocompromised conditions such as malignancy, autoimmune disease, chronic alcohol intake, poorly controlled diabetes and long-term steroid use. Malakoplakia can occur at various sites, most commonly in the genitourinary tract including urinary bladder and the ureter. Renal parenchymal involvement is relatively uncommon, accounting for 15% of all malakoplakia. A few cases of renal malakoplakia have been reported in Korea, and only one case was accompanied by acute kidney injury. Here we report an 80-year-old female patient with renal parenchymal malakoplakia and acute interstitial nephritis presented as acute kidney injury with literature review.