ABSTRACT
PURPOSE: The intensity of adjuvant treatment for pancreatic ductal adenocarcinomas (PDACs) has not been stratified according to the risk after resection. This study was designed to identify patients with PDACs in whom the current S-1 adjuvant treatment is ineffective. METHODS: This single-center, retrospective study included patients who underwent pancreatectomy for PDACs from 2009 to 2020 at Sendai Open Hospital and were receiving S-1 adjuvant treatment. The independent risk factors for recurrence and survival were determined by using a Cox proportional hazards regression model. The effects of S-1 adjuvant treatment and detailed patterns of recurrence were evaluated in patients with high-risk factors. RESULTS: Overall, 118 patients with PDAC received S-1 adjuvant treatment. Postoperative nonnormalized carbohydrate antigen (CA19-9) was a predictive risk factor for recurrence (p < 0.010; hazard ratio [HR], 3.87; 95% confidence interval [CI], 2.26-6.62) and survival (p = 0.008; HR, 2.25; 95% CI, 1.24-4.11) after S-1 adjuvant treatment. In 24 patients with nonnormalized postoperative CA19-9, S-1 monotherapy was ineffective in preventing recurrence, even during the treatment period, compared with that noted in patients who did not receive adjuvant treatment. The recurrence rate during adjuvant treatment was 41.7%; in all cases, recurrence was caused by distant metastasis. The total recurrence rate was up to 95.8%, and distant recurrence was especially frequent. CONCLUSIONS: The current S-1 adjuvant treatment regimen is ineffective for patients with postoperative nonnormalized CA19-9. The postoperative CA19-9 level may be a good indicator for further aggressive treatment. This study may lead to further discussions on intensity stratification of adjuvant treatments for PDAC.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Retrospective Studies , CA-19-9 Antigen , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/surgery , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Chemotherapy, Adjuvant , Pancreatectomy , Carbohydrates , Neoplasm Recurrence, Local/pathology , PrognosisABSTRACT
PURPOSE: The importance of tumor markers is well established; yet little is known about their prognostic value for patients with obstructive colorectal cancer (OCRC). We investigated the clinical significance of carcinoembryonic antigen (CEA) and CA 19-9 levels in patients with non-metastatic OCRC, who underwent insertion of a self-expandable metallic stent and curative surgery. METHODS: Clinical data on 91 patients with OCRC were analyzed retrospectively to evaluate the associations of preoperative serum values of tumor makers with short- and long-term outcomes. RESULTS: The 91 patients comprised 53 men and 38 women, with a median age of 71Ā years. Twelve patients had an elevated preoperative CA 19-9 level. Multivariate analyses revealed that an elevated CA 19-9 level was independently associated with poor disease-free survival (DFS) [hazard ratio (HR) = 4.57, 95% confidence interval (CI) 2.06-10.14, P < 0.001] and overall survival (HR = 4.06, 95% CI 1.46-11.24, P = 0.007). A CEA level > 5Ā ng/ml had no prognostic value, whereas a CEA level > 10.8Ā ng/ml was significantly associated with worse DFS (P = 0.032). CONCLUSION: Measuring the CA 19-9 level concomitantly with the CEA level for patients with advanced CRC, including OCRC, may provide a valuable means to improve prognostication.
ABSTRACT
PURPOSE: Sarcopenia influences the short- and long-term outcomes of various medical conditions including malignancy. Ishii's screening test estimates the probability of sarcopenia based on a score calculated by three simple variables: age, grip strength, and calf circumference. We investigated the clinical significance of Ishii's score for patients with non-metastatic obstructive colorectal cancer (OCRC) who underwent curative surgery after intraluminal decompression. METHODS: Ishii's score was calculated in 79 patients with OCRC. Muscle volume loss and decreased muscle quality were evaluated by computed tomography (CT) images as skeletal muscle index (SMI) and intramuscular adipose tissue content (IMAC), respectively. RESULTS: There were 46 men and 33 women, with a median age of 70Ā years old. The cutoff value for Ishii's score was 155.1 and 15 patients were in the high-score group. The high-score group was significantly associated with worse time to recurrence (TTR) and overall survival (OS), and a high Ishii's score was an independent negative prognostic factor for TTR (hazard ratio = 2.93, P = 0.015). A high Ishii's score was significantly associated with a low SMI value but not with the IMAC value. CONCLUSION: A high Ishii's score was independently associated with poorer TTR in patients with non-metastatic OCRC.
ABSTRACT
PURPOSE: Inflammation is one of the hallmarks of cancer, and inflammation-based markers that are calculated easily from laboratory results have shown predictive abilities. We investigated the prognostic values of the preoperative platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and pan-immune-inflammation value (PIV) in patients with non-metastatic obstructive colorectal cancer (OCRC) and a self-expandable metallic stent inserted as a bridge to curative surgery. METHODS: The subjects of this retrospective study were 86 patients with pathological stage I to III OCRC. We examined the associations of these biomarkers with short- and long-term outcomes. RESULTS: Multivariate analyses revealed that a preoperative PLRĀ <Ā 149, SII < 597, and PIV < 209 were independently associated with poorer relapse-free survival (RFS) (P = 0.007, P < 0.001, and P = 0.002, respectively) and that a PIV < 209 was independently associated with poorer cancer-specific survival (P = 0.030). A platelet count < 240 was significantly associated with worse RFS, whereas the lymphocyte count was not. Pre-stenting PLR < 221 was an independent poor prognostic factor for RFS (P = 0.045). CONCLUSION: This study showed that decreased preoperative PLR, SII, PIV, and pre-stenting PLR were associated with poorer RFS, contrary to the findings of most previous studies. Our results suggest that platelets and obstruction contributed primarily to the opposite relationships, which might provide new insight into the possible pathophysiology of platelet-tumor interactions generated in the OCRC environment.
Subject(s)
Colorectal Neoplasms , Neoplasm Recurrence, Local , Stents , Humans , Colorectal Neoplasms/surgery , Inflammation , Lymphocytes , Neoplasm Recurrence, Local/surgery , Neutrophils , Prognosis , Retrospective StudiesABSTRACT
Importance: For patients with RAS wild-type metastatic colorectal cancer, adding anti-epidermal growth factor receptor (anti-EGFR) or anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined. Objective: To evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) vs bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic colorectal cancer. Design, Setting, and Participants: Randomized, open-label, phase 3 clinical trial at 197 sites in Japan in May 2015-January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic colorectal cancer (final follow-up, January 14, 2022). Interventions: Panitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days. Main Outcomes and Measures: The primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resection rate. Results: In the as-treated population (n = 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had left-sided tumors. Median follow-up was 61 months. Median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio [HR] for death, 0.82; 95.798% CI, 0.68-0.99; P = .03) and 36.2 vs 31.3 months, respectively, in the overall population (HR, 0.84; 95% CI, 0.72-0.98; P = .03). Median progression-free survival for panitumumab vs bevacizumab was 13.1 vs 11.9 months, respectively, for those with left-sided tumors (HR, 1.00; 95% CI, 0.83-1.20) and 12.2 vs 11.4 months overall (HR, 1.05; 95% CI, 0.90-1.24). Response rates with panitumumab vs bevacizumab were 80.2% vs 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI, 4.4%-17.9%) and 74.9% vs 67.3% overall (difference, 7.7%; 95% CI, 1.5%-13.8%). Median duration of response with panitumumab vs bevacizumab was 13.1 vs 11.2 months for left-sided tumors (HR, 0.86; 95% CI, 0.70-1.10) and 11.9 vs 10.7 months overall (HR, 0.89; 95% CI, 0.74-1.06). Curative resection rates with panitumumab vs bevacizumab were 18.3% vs 11.6% for left-sided tumors; (difference, 6.6%; 95% CI, 1.0%-12.3%) and 16.5% vs 10.9% overall (difference, 5.6%; 95% CI, 1.0%-10.3%). Common treatment-emergent adverse events were acneiform rash (panitumumab: 74.8%; bevacizumab: 3.2%), peripheral sensory neuropathy (panitumumab: 70.8%; bevacizumab: 73.7%), and stomatitis (panitumumab: 61.6%; bevacizumab: 40.5%). Conclusions and Relevance: Among patients with RAS wild-type metastatic colorectal cancer, adding panitumumab, compared with bevacizumab, to standard first-line chemotherapy significantly improved overall survival in those with left-sided tumors and in the overall population. Trial Registration: ClinicalTrials.gov Identifier: NCT02394795.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bevacizumab , Colorectal Neoplasms , Panitumumab , Aged , Female , Humans , Male , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Bevacizumab/therapeutic use , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Fluorouracil/administration & dosage , Leucovorin/administration & dosage , Panitumumab/administration & dosage , Panitumumab/adverse effects , Panitumumab/therapeutic use , Oxaliplatin/administration & dosage , ErbB Receptors/antagonists & inhibitors , Vascular Endothelial Growth Factors/antagonists & inhibitorsABSTRACT
This multicenter single-arm, phase II study evaluated the efficacy and safety of uninterrupted panitumumab usage combined with cytotoxic doublets for unresectable/metastatic colorectal cancer (mCRC). Additionally, clinical value of the RAS/BRAF mutation status in circulating cell-free DNA (ccfDNA) was evaluated; this evaluation was measured independently of the protocol treatment. Eligible patients with RAS wild-type mCRC who had received the first-line panitumumab plus FOLFOX treatment were recruited and administered continuous panitumumab combined with FOLFIRI. Progression-free survival (PFS) at 6Ā months was the primary endpoint, with threshold and expected values of 35% and 50%, respectively. In total, 54 patients were enrolled between October 2017 and October 2019. The crude 6-month PFS rate was 37.0%, with a 4.8-month median PFS. The response rate and disease control rate were 16.7% and 50.0%, respectively. Notably, of the 54 participants, 17 showed RAS/BRAF mutations until the end of the protocol treatment and of the 22 patients with progressive disease as their best response, 10 possessed RAS/BRAF mutations in their plasma ccfDNA at baseline. The median PFS significantly differed among patients harboring tumors with BRAF and RAS mutations and those with wild-type tumors. In conclusion, our study failed to show the expected efficacy of the continuous panitumumab use in the second-line treatment. Liquid biopsy discriminated the duration of PFS according to the mutation status. The effectiveness of continuous treatment with panitumumab should be evaluated in patients with RAS/BRAF wild-type mCRC determined by liquid biopsy at the start of the second-line treatment.
Subject(s)
Cell-Free Nucleic Acids , Colonic Neoplasms , Colorectal Neoplasms , Rectal Neoplasms , Humans , Panitumumab/therapeutic use , Proto-Oncogene Proteins B-raf/genetics , Leucovorin/adverse effects , Camptothecin/adverse effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Fluorouracil/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Mutation , Colonic Neoplasms/drug therapy , Rectal Neoplasms/drug therapyABSTRACT
PURPOSE: The prognostic significance of the mean corpuscular volume (MCV) and red cell distribution width (RDW) in patients with malignancy have not been intensely investigated and are largely overlooked. We, therefore, investigated the clinical significance of MCV and RDW in non-metastatic obstructive colorectal cancer (OCRC) patients with a self-expandable metallic stent inserted as a bridge to curative surgery. METHODS: Eighty-five pathological stage II and III OCRC patients were retrospectively evaluated. The associations of the preoperative MCV and RDW values with short- and long-term outcomes were examined. RESULTS: There were 50 males and 35 females, and the median age was 71Ā years old. The median interval between stenting and surgery was 17Ā days, and the median postoperative hospital stay was 16Ā days. Fifty-six patients were in the MCV ≥ 87 group, and 47 were in the RDW ≥ 13.8 group. Multivariate analyses revealed the MCV ≥ 87 status to be independently associated with a poor relapse-free survival (hazard ratio [HR] = 4.70, 95% confidence interval [CI] 1.52-14.58, P = 0.007). The RDW ≥ 13.8% was an independent predictor of postoperative infectious complications (HR = 7.28, 95% CI 1.24-42.70, P = 0.028). CONCLUSION: The MCV and RDW are simple but strong predictors of postoperative outcomes in OCRC patients.
Subject(s)
Colorectal Neoplasms , Erythrocyte Indices , Male , Female , Humans , Aged , Prognosis , Retrospective Studies , Postoperative Complications/epidemiology , Stents , Colorectal Neoplasms/surgeryABSTRACT
PURPOSE: Intestinal decompression using self-expandable metallic colonic stents (SEMSs) as a bridge to surgery is now considered an attractive alternative to emergency surgery. However, data regarding the optimal timing of surgery after stenting are limited. METHODS: We investigated the impact of the interval between stenting and surgery on short- and long-term outcomes in 92 obstructive colorectal cancer (OCRC) patients who had a SEMS inserted and subsequently received curative surgery. RESULTS: The median age of the patients was 70.5Ā years, and the median interval between SEMS insertion and the surgery was 17 (range 5-47) days. There were 35 postoperative complications, including seven major postoperative complications. An interval of more than 16Ā days was an independent predictor of a poor relapse-free survival (hazard ratio [HR] = 3.12, 95% confidence interval [CI] 1.24-7.81, p = 0.015). An interval of more than 35Ā days was independently associated with major postoperative complications (HR = 16.6, 95% CI 2.21-125, p = 0.006). CONCLUSION: A longer interval between stenting and surgery significantly compromised the short- and long-term outcomes. Surgery within 16Ā days after stenting might help maximize the benefit of SEMS without interfering with short- and long-term outcomes.
Subject(s)
Colorectal Neoplasms , Intestinal Obstruction , Aged , Humans , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Neoplasm Recurrence, Local , Retrospective Studies , Stents/adverse effects , Treatment OutcomeABSTRACT
PURPOSE: The Controlling Nutritional Status (CONUT) Score, originally developed as a nutritional screening tool, is a cumulative score calculated from the serum albumin level, total cholesterol level, and total lymphocyte count. Previous studies have demonstrated that the score has significant prognostic value in various malignancies. We investigated the relationship between the CONUT score and long-term survival in obstructive colorectal cancer (OCRC) patients who underwent self-expandable metallic colonic stent placement and subsequently received curative surgery. METHODS: We retrospectively analyzed 57 pathological stage II and III OCRC patients between 2013 and 2019. The associations between the preoperative CONUT score and clinicopathological factors and patient survival were evaluated. RESULTS: A receiver operating characteristic curve analysis revealed that the optimal cut-off value for the CONUT score was 7. A CONUT score of ≥ 7 was significantly associated with elevated CA19-9 level (p = 0.03). Multivariate analyses revealed that a CONUT score of ≥ 7 was independently associated with cancer-specific survival (hazard ratio [HR] = 10.2, 95% confidence interval [CI] 1.2-85.9, p = 0.03) and disease-free survival (HR = 7.1, 95% CI 2.3-21.7, p = 0.0006). CONCLUSION: The results demonstrated that the CONUT score was a potent prognostic indicator. Evaluating the CONUT score might result in more precise patient assessment and tailored treatment.
Subject(s)
Colorectal Neoplasms/mortality , Colorectal Neoplasms/surgery , Nutritional Status , Self Expandable Metallic Stents , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Cholesterol/blood , Female , Humans , Male , Middle Aged , Palliative Care , Prognosis , Retrospective Studies , Serum Albumin , Survival RateABSTRACT
The number of elderly patients and colorectal cancer patients is increasing, so laparoscopic surgery for colorectal cancer in elderly patients is suspected to increase. In 456 patients who underwent laparoscopic surgery for colorectal cancer, we investigated whether laparoscopic surgery for elderly patients with colon cancer patients could be performed equally compared to non-elderly patients. Preoperative ASA-PS was slightly poorer in elderly patients. There was no significant difference in pStage. The 5-year overall survival rate was lower in the elderly, but there were no significant differences in blood loss, operation time, postoperative hospital stays and incidence of complications of Clavien-Dindo classification grade 3 or higher. It was suggested that laparoscopic surgery for elderly patients with colorectal cancer may be safely performed compared with non-elderly patients.
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Laparoscopy , Aged , Colonic Neoplasms/surgery , Colorectal Neoplasms/surgery , Humans , Middle Aged , Operative Time , Postoperative Complications , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: Oxaliplatin, one of the key cytotoxic drugs for colorectal cancer, frequently causes peripheral neuropathy which leads to dose modification and decreased patients' quality of life. However, prophylactic or therapeutic measures have not yet been established. Orally administered amino acids, cystine and theanine, promoted the synthesis of glutathione which was one of the potential candidates for preventing the neuropathy. The aim of this study was to determine whether daily oral administration of cystine and theanine attenuated oxaliplatin-induced peripheral neuropathy (OXLIPN). METHODS: Twenty-eight colorectal cancer patients who received infusional 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) therapy were randomly and evenly assigned to the cystine and theanine group and the control group. OXLIPN was assessed up to the sixth course using original 7-item questionnaire as well as Common Terminology Criteria for Adverse Events (CTCAE) grading scale. RESULTS: Neuropathy scores according to our original questionnaire were significantly smaller in the cystine and theanine group at the fourth (p = 0.026), fifth (p = 0.029), and sixth course (p = 0.038). Furthermore, significant differences were also observed in CTCAE neuropathy grades at the fourth (p = 0.037) and the sixth course (p = 0.017). There was one patient in each group who required dose reduction due to OXLIPN. Except for neurotoxicity, no significant differences were noted in the incidence of adverse events, and the total amount of administered oxaliplatin. CONCLUSION: The results demonstrated the daily oral administration of cystine and theanine attenuated OXLIPN.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/drug therapy , Glutamates/administration & dosage , Oxaliplatin/adverse effects , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/prevention & control , Administration, Oral , Aged , Cystine/administration & dosage , Female , Fluorouracil/adverse effects , Humans , Leucovorin/adverse effects , Male , Middle Aged , Organoplatinum Compounds/adverse effects , Oxaliplatin/administration & dosage , Pilot Projects , Quality of LifeABSTRACT
PURPOSE: Inflammation-based markers predict the long-term outcomes of various malignancies. We investigated the relationship between the modified Glasgow prognostic score (mGPS) and the long-term outcomes of obstructive colorectal cancer in patients who underwent self-expandable metallic colonic stent placement and subsequently received curative surgery. METHODS: We retrospectively analyzed 63 consecutive patients with pathological stage II and III obstructive colorectal cancer from 2013 to 2018. The mGPS was calculated before stenting and surgery, and the difference of the scores was defined as the d-mGPS. RESULTS: All d-mGPS = 2 patients were > 70Ā years of age (p = 0.01). Postoperative complications were more common in the preoperative mGPS = 2 group (p = 0.02). The postoperative hospital stay was significantly longer in the mGPS = 2 group (p = 0.007). Multivariate analyses revealed that d-mGPS was an independent prognostic factor for overall survival (OS) (hazard ratio [HR] = 9.18, p = 0.004) and cancer-specific survival (HR = 9.98, p = 0.01). Preoperative mGPS = 2 was significantly associated with poor OS (HR = 5.53, p = 0.04). CONCLUSION: The results indicated that mGPS might serve as a valuable indicator of the immunonutritional status of preoperative patients, and a preoperative change of the status might affect the long-term outcomes of patients with obstructive colorectal cancer.
Subject(s)
Colorectal Neoplasms/surgery , Glasgow Outcome Scale , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Stents , Aged , Colorectal Neoplasms/complications , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Humans , Neoplasm Staging , Nutritional Status , Predictive Value of Tests , Preoperative Period , Time FactorsABSTRACT
PURPOSE: Inflammation-based markers predict long-term outcomes of various malignancies. We investigated the relationship between these markers and the long-term survival in obstructive colorectal cancer (OCRC) patients with self-expandable metallic colonic stents (SEMSs) who subsequently received curative surgery. METHODS: We retrospectively analyzed 72 consecutive pathological stage II and III OCRC patients between 2013 and 2019. The prognostic significance of the prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), and platelet-lymphocyte ratio (PLR) was evaluated. RESULTS: The overall survival (OS), cancer-specific survival, and disease-free survival (DFS) were significantly shorter in the PNI < 35 group than in the PNI ≥ 35 group (p = 0.006, p < 0.001, and p = 0.003, respectively), and multivariate analyses revealed the PNI to be the only inflammation-based marker independently associated with the survival. A PNI < 35 was significantly associated with an elevated CA 19-9 level (p = 0.04) and longer postoperative hospital stay (p = 0.03). Adjuvant chemotherapy was also significantly associated with the OS (p = 0.040) and DFS (p = 0.011) in multivariate analyses. CONCLUSION: The results showed that the PNI was a potent prognostic indicator. For OCRC patients, both systemic inflammation and the nutrition status seem to be important for predicting the prognosis, and administering adjuvant chemotherapy was very important.
Subject(s)
Colorectal Neoplasms/surgery , Nutrition Assessment , Nutritional Status , Adult , Aged , Aged, 80 and over , CA-19-9 Antigen , Chemotherapy, Adjuvant , Colorectal Neoplasms/complications , Colorectal Neoplasms/mortality , Disease-Free Survival , Female , Humans , Inflammation , Intestinal Obstruction/etiology , Intestinal Obstruction/mortality , Intestinal Obstruction/surgery , Length of Stay , Male , Middle Aged , Prognosis , Retrospective Studies , Self Expandable Metallic StentsABSTRACT
A 67-year-old man with complaints of upper abdominal pain visited a clinic and was diagnosed with type 3 gastric cancer. Contrasted-enhanced CT revealed gastric wall thickening and extensive metastatic lymph nodes particularly around the celiac artery and also invasion to pancreas. He was diagnosed with cT4b, cN2, cM0, cStage Ć¢Ā Ā¢B and we treated with neoadjuvant chemotherapy(NAC)consisting of 4 courses of S-1 and cisplatin regimen. After the NAC, primary cancer and metastatic lymph nodes were reduced remarkably. A curative operation could be performed and the histopathological examination showed"Grade 3, pathological complete response".
Subject(s)
Neoadjuvant Therapy , Stomach Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cisplatin/therapeutic use , Drug Combinations , Gastrectomy , Humans , Male , Oxonic Acid/therapeutic use , Stomach Neoplasms/drug therapy , Stomach Neoplasms/surgery , Tegafur/therapeutic useABSTRACT
A 59-year-old man with chief complaints of right-sided rib pain and fever was admitted to our hospital. A type 2 tumor in the ascending colon was revealed by total colonoscopy. Computed tomography examination revealed multiple tumors in the liver. The white blood cell count was high as 13,740/ĀµL. Chemotherapy was planned after treatment with antibiotics, but it was not successful. Right colectomy was performed for infection control. mFOLFOX6 therapy was performed, but liver metastases progressed rapidly, and he died on the 39th postoperative day. The immunohistochemistry revealed G-CSF producing colon cancer. G-CSF producing colon cancer progresses rapidly with poor prognosis. It is necessary to think carefully about indication of surgery and chemotherapy.
Subject(s)
Colon, Ascending , Colonic Neoplasms , Colon, Ascending/surgery , Colonic Neoplasms/drug therapy , Colonic Neoplasms/surgery , Granulocyte Colony-Stimulating Factor , Granulocytes , Humans , Immunohistochemistry , Male , Middle AgedABSTRACT
Certain genetic alterations and right-sided primary tumor location are associated with resistance to anti-epidermal growth factor (EGFR) treatment in metastatic colorectal cancer (mCRC). The phase 3 PARADIGM trial (n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. This prespecified exploratory biomarker analysis of PARADIGM (n = 733) evaluated the association between circulating tumor DNA (ctDNA) gene alterations and efficacy outcomes, focusing on a broad panel of gene alterations associated with resistance to EGFR inhibition, including KRAS, NRAS, PTEN and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK, RET and NTRK1 fusions. Overall survival was prolonged with panitumumab plus modified FOLFOX6 versus bevacizumab plus modified FOLFOX6 in patients with ctDNA that lacked gene alterations in the panel (that is, negative hyperselected; median in the overall population: 40.7 versus 34.4 months; hazard ratio, 0.76; 95% confidence interval, 0.62-0.92) but was similar or inferior with panitumumab in patients with ctDNA that contained any gene alteration in the panel (19.2 versus 22.2 months; hazard ratio, 1.13; 95% confidence interval, 0.83-1.53), regardless of tumor sidedness. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795 .
Subject(s)
Colonic Neoplasms , Colorectal Neoplasms , Rectal Neoplasms , Humans , Panitumumab/therapeutic use , Bevacizumab/therapeutic use , Antibodies, Monoclonal/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colonic Neoplasms/drug therapy , Rectal Neoplasms/drug therapy , Biomarkers , ErbB Receptors/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Proto-Oncogene Proteins p21(ras)ABSTRACT
The interim analysis of the CIRCULATE-Japan GALAXY observational study demonstrated the association of circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) detection with recurrence risk and benefit from adjuvant chemotherapy (ACT) in resectable colorectal cancer (CRC). This updated analysis with a 23-month median follow-up, including 2,240 patients with stage II-III colon cancer or stage IV CRC, reinforces the prognostic value of ctDNA positivity during the MRD window with significantly inferior disease-free survival (DFS; hazard ratio (HR): 11.99, P < 0.0001) and overall survival (OS; HR: 9.68, P < 0.0001). In patients who experienced recurrence, ctDNA positivity correlated with shorter OS (HR: 2.71, P < 0.0001). The significantly shorter DFS in MRD-positive patients was consistent across actionable biomarker subsets. Sustained ctDNA clearance in response to ACT was an indicator of favorable DFS and OS compared to transient clearance (24-month DFS: 89.0% versus 3.3%; 24-month OS: 100.0% versus 82.3%). True spontaneous clearance rate with no clinical recurrence was 1.9% (2/105). Overall, our findings provide evidence for the utility of ctDNA monitoring for post-resection recurrence and mortality risk stratification that could be used for guiding adjuvant therapy.
ABSTRACT
Objectives: The geriatric nutritional risk index (GNRI) is a nutrition-related risk index calculated easily from serum albumin and the ratio of body weight to ideal body weight. We investigated the prognostic values of the GNRI in elderly patients with obstructive colorectal cancer (OCRC) who had a self-expandable metallic stent inserted as a bridge to curative surgery. Methods: We retrospectively evaluated 61 patients aged ≥65 years with pathological stage I to III OCRC. Associations of preoperative GNRI and pre-stenting GNRI (ps-GNRI) with short- and long-term outcomes were examined. Results: Multivariate analyses revealed GNRI of <85.3 and ps-GNRI of <92.9 were independently associated with worse cancer-specific survival (CSS; P = 0.016, and P = 0.041, respectively), and overall survival (OS; P = 0.020, and P = 0.024, respectively). A ps-GNRI of <92.9 was correlated with poorer relapse-free survival (RFS) only in the univariate analysis (P = 0.034). For the OCRC cohort without age restriction (n = 86), GNRI of <85.3 and ps-GNRI of <92.9 were independently associated with worse CSS (P = 0.021), and OS (P = 0.023), respectively. In univariate analysis, ps-GNRI of <92.9 was significantly correlated with poorer RFS (P = 0.006). Moreover, ps-GNRI of <92.9 was significantly associated with Clavien-Dindo grade of ≥III postoperative complications (P = 0.037), anastomotic leak (P = 0.032), infectious complications (P = 0.002), and longer postoperative hospital stay (17 days vs. 15 days; P = 0.048). Conclusions: In OCRC patients, decreased preoperative and pre-stenting GNRI were significantly correlated with poorer survival, and decreased pre-stenting GNRI was significantly associated with worse short- and long-term outcomes.