Determinants of Metastatic Colorectal Cancer With Permanent Liver- Limited Disease.

Colorectal cancer (CRC) is a complex and genetically heterogeneous disease presenting a specific metastatic pattern, with the liver being the most common site of metastasis. Around 20%-25% of patients with CRC will develop exclusively hepatic metastatic disease throughout their disease history. With its specific characteristics and therapeutic options, liver-limited disease (LLD) should be considered as a specific entity. The identification of these patients is particularly relevant in view of the growing interest in liver transplantation in selected patients with advanced CRC. Identifying why some patients will develop only LLD remains a challenge, mainly because of a lack of a systemic understanding of this complex and interlinked phenomenon given that cancer has traditionally been investigated according to distinct physiological compartments. Recently, multidisciplinary efforts and new diagnostic tools have made it possible to study some of these complex issues in greater depth and may help identify targets and specific treatment strategies to benefit these patients. In this review we analyze the underlying biology and available tools to help clinicians better understand this increasingly common and specific disease.

Therapeutic Patterns and Clinical Outcomes in Limited Disease Small Cell Lung Cancer: A Decade of Analysis at a Tertiary Cancer Center.

In this study, we investigated the outcomes and factors influencing treatment efficacy in 93 patients with limited disease small cell lung cancer (LD-SCLC), with a median age of 64 years. We focused on the impact of chemotherapy regimens, prophylactic cranial irradiation (PCI), and patient-related variables. The median follow-up for OS was 17.3 months. We observed a statistically significant difference in PFS between LD-SCLC patients treated with cisplatin and etoposide (EP) and those treated with carboplatin and etoposide (CP) (PFS: EP 13.63 months vs. CP 6.54 months, p < 0.01). Patients treated with EP had better overall survival (OS) than CP-treated patients (OS: EP 26.9 months vs. CP 16.16 months, p < 0.01). Concomitant chemotherapy was associated with improved PFS (p = 0.003) and OS (p = 0.002). Patients receiving PCI showed superior OS (p = 0.05) and a trend towards improved PFS (p = 0.057). Female gender was associated with better OS (p = 0.025). Most patients had an ECOG performance status of 0 (71%). This real-world study underscores the importance of multidisciplinary LD-SCLC management, emphasizing the roles of chemotherapy, radiotherapy, and PCI. These findings inform personalized treatment strategies and emphasize the need for prospective trials to validate these results and optimize LD-SCLC treatment.

Predicting disease recurrence in limited disease small cell lung cancer using cell-free DNA-based mutation and fragmentome analyses.

Background: Limited disease (LD) small cell lung cancer (SCLC) treated with definitive concurrent chemoradiotherapy (CCRT) potentially experience disease recurrence. We investigated the feasibility of circulating-tumor DNA (ctDNA)-based genomic and fragmentome analyses to assess the risk of recurrence. Methods: Targeted sequencing was conducted using pre-treatment and on-treatment blood samples from definitive CCRT-treated patients with LD-SCLC (n=50). Based on 12-month recurrence-free survival (RFS), patients were categorized into persistent-response (PeR, n=29) and non-PeR (n=21) groups. Fragmentome analysis was conducted using ctDNA fragments of different lengths: P1 (100-155 bp) and P2 (160-180 bp). Results: Patients with TP53 (n=15) and RB1 (n=11) mutation in on-treatment samples demonstrated significantly shorter RFS than patients with wild-type (WT) (P=0.05, P=0.0014, respectively). Fragmentome analysis of all available on-treatment samples (n=26) revealed that the non-PeR group (n=10) had a significantly higher P1 range (P=0.003) and lower P2 range (P=0.002). The areas under the curves for P1, P2, and the fragmentation ratio (P1/P2) in distinguishing the PeR and non-PeR were 0.850, 0.725, and 0.900, respectively. Using optimal cut-off, longer RFSs were found with the low-fragmentation-ratio group than with the high-fragmentation-ratio group (not reached vs. 7.6 months, P=0.002). Patients with both WT RB1 and a low-fragmentation-ratio (n=10) showed better outcomes than patients with both mutated RB1 and a high-fragmentation-ratio (n=10; hazard ratio, 7.55; 95% confidence interval: 2.14-26.6; P=0.002). Conclusions: RB1 mutations and high fragmentation ratios correlated with early disease recurrence. Analyzing ctDNA could help in predicting early treatment failure and making clinical decisions for high-risk patients.

Comorbidity in limited disease small-cell lung cancer: Age-adjusted Charlson comorbidity index and its association with overall survival following chemoradiotherapy.

Background: Combined, platinum-based thoracic chemoradiotherapy (TCR) is the current state-of-the-art treatment for patients with limited disease (LD) small-cell lung cancer (SCLC). There is only limited data available regarding the effect of comorbidities on survival following TRC. The purpose of this study is to assess the age-adjusted Charlson comorbidity index (ACCI) as a predictor of overall survival in LD-SCLC patients undergoing TCR. Patients and methods: We retrospectively analyzed 367 SCLC patients diagnosed with LD-SCLC who received TCR between 2003 and 2017. We evaluated the ACCI (n = 348) as a predictor of overall survival (OS). In this cohort, 322 patients (88%) received platinum-based TCR (either cisplatin or carboplatin), and 37 (10%) patients received vincristine based TCR. Median radiation dose was 60 Gy (range 24-66 Gy). Additionally, 83% of patients (n = 303) received prophylactic cranial irradiation (PCI, 30 Gy in 2 Gy fractions). Kaplan-Meier survival analysis was performed for OS. For comparison of survival curves, Log-rank (Mantel-Cox) test was used. Univariate and multivariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS. Results: Patients with an ACCI > 6 had a significantly shorter OS compared with patients with an ACCI ≤ 6 (median 11 vs. 20 months; p = 0.005). Univariate analysis for OS revealed a statistically significant effect for ACCI > 6 (HR 1.7; 95% CI 1.2-2.4; p = 0.003), PCI (HR 0.5; 95% CI 0.3-0.7; p < 0.001), and Karnofsky performance status ≤ 70% (KPS) (HR 1.4; 95% CI 1.1-1.90; p = 0.015). In multivariate analysis, OS was significantly associated with PCI (HR 0.6; 95% CI 0.4-0.9; p = 0.022) and ACCI > 6 (HR 1.5; 95% CI 1.0-2.1; p = 0.049). Conclusion: Comorbidity is significantly associated with survival in patients with LD-SCLC undergoing TCR. The ACCI may be a valuable tool to identify patients with a shorter survival and thus might be used for risk stratification and oncological decision making.

Pneumomediastinum secondary to diabetes ketoacidosis in high altitude: a case report / 中国综合临床

Diabetic ketoacidosis (DKA), a serious acute complication of diabetes mellitus, mainly manifests as hyperglycemia, ketosis, and acidosis. It is a metabolic syndrome resulting from insulin deficiency and increased insulin-antagonistic hormone levels. While type 2 diabetes mellitus complicated by DKA is relatively uncommon, secondary pneumomediastinum in DKA is extremely rare. Following alveolar rupture, air can travel through various routes to reach the hilum, causing anterior, middle, or posterior pneumomediastinum or even leading to intracranial epidural pneumatosis. The diagnosis of pneumomediastinum is mainly dependent on chest computed tomography findings. After the successful treatment of DKA, pneumomediastinum usually resolves spontaneously within 5-10 days with a good prognosis. One DKA patient admitted to Dege County People's Hospital developed Kussmaul respirations, followed by an increase in intra-alveolar pressure, an elevation in intra and extra-alveolar pressure difference, and protein decomposition in the alveolus wall, which promoted alveolar rupture and induced mediastinal emphysema. After rapid fluid replacement, blood glucose control with insulin, and maintenance of acid-base balance (correction DKA), the mediastinal emphysema was spontaneously absorbed. Through the analysis of the clinical data of this case, the purpose is to improve the clinicians' internal understanding of the relationship between mediastinal emphysema and DKA, avoid over-examination and over-treatment, and provide strategies for correct diagnosis and treatment.

Epipericardial fat necrosis in a patient with sudden chest pain.

Epipericardial fat necrosis (EFN) may be considered in the differential diagnosis of chest pain. Clinicians should be kept in mind that EFN is self-limiting and is often followed up with imaging.

Efficacy evaluation of surgery combined with chemotherapy for stage IIIA small cell lung cancer patients: a retrospective analysis.

Background: The efficacy of surgery in combination of chemotherapy for stage IIIA small cell lung cancer (IIIA-SCLC) is controversial. The aim of the present study was to analyze the efficacy of surgery combined with chemotherapy, especially in the setting of neoadjuvant chemotherapy (NAC) followed by surgery for IIIA-SCLC. Methods: Between 2004 and 2015, we reviewed 2,199 chemotherapy-treated stage IIIA (N1/2) SCLC cases in the Surveillance, Epidemiology, and End Results (SEER) database, and 32 NAC + intentional radical resection-treated, centrally-located IIIA-SCLC cases at Shanghai Pulmonary Hospital (SPH). Outcomes were compared between surgically and non-surgically treated patients from the SEER database after propensity score matching (PSM), and comparing lobectomy/bi-lobectomy and pneumonectomy patients from SPH. Prognostic factors were evaluated by Kaplan-Meier method and the Cox proportional hazards regression model. Results: There was significantly higher overall survival (OS) in surgically treated IIIA-SCLC patients (OS, 44.8 vs. 21.2 months, P=0.048), and similar efficacy was observed between sub-lobectomy and lobectomy/bi-lobectomy patients (OS: 55.6 vs. 30.3 months, P=0.167) in SEER database. At SPH, significantly higher OS was associated with T1 stage (before NAC: T1 vs. T2-4, 48.7 vs. 32.2 months, P=0.025; after NAC: T1 vs. T2-4, 42.7 vs. 21.3 months, P=0.048). Female sex [hazard ratio (HR): 0.078, P=0.009], T1 stage (HR: 13.048, P=0.026), and pneumonectomy (HR: 0.095, P=0.009) were independent prognostic factors for IIIA-SCLC patients who received NAC + intentional radical resection. Conclusions: For stage IIIA SCLC patients, complete resection combined with chemotherapy might improve the prognosis than patients without surgery. Post-NAC lobectomy was not found to be superior to sub-lobectomy, while pneumonectomy was considered suitable for central-type IIIA-SCLC patients after NAC treatment.

＜Editors' Choice＞ Elective nodal irradiation versus involved field radiotherapy for limited disease small cell lung cancer: a single-institution experience.

Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with limited-disease small cell lung cancer (LD-SCLC). However, no solid consensus exists on their optimal target volume. The current study aimed to assess the clinical outcomes of patients with LD-SCLC who received definitive ENI or IFRT. A retrospective single-institution study of patients who received definitive radiotherapy between 2008 and 2020 was performed. All patients underwent whole-body positron emission tomography/computed tomography before three-dimensional conformal radiotherapy. Among the 37 patients analyzed, 22 and 15 received ENI and IFRT, respectively. The thoracic radiotherapy dose was mostly either 60 Gy in 30 fractions delivered in 2-Gy fractions once daily or 45 Gy in 30 fractions delivered in 1.5-Gy fractions twice daily. The median follow-up period was 21.4 months. A total of 12 patients (32%) experienced locoregional relapse: 10 within and 2 outside the irradiation fields. One patient in the IFRT group experienced isolated nodal failure. Differences in locoregional relapse-free, progression-free, and overall survival rates between ENI and IFRT were not significant. Overall, IFRT did not promote a significant increase in locoregional recurrence compared to ENI. Our findings suggested the utility of IFRT in standard clinical practice and support its use for patients with LD-SCLC.

Syndrome of Inappropriate Antidiuretic Hormone Secretion as the Initial Presentation in a Patient with Stage I Small-cell Lung Cancer.

A 67-year-old man with a history of esophageal cancer resection was referred to our hospital because of nausea and appetite loss. Laboratory findings showed severe hyponatremia and were compatible with syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Chest computed tomography (CT) revealed a nodule measuring 13 mm in the lower lobe of the right lung. Right thoracotomy was performed, and the histopathological diagnosis was small-cell lung cancer (T1bN0M0; Stage 1b). Although SIADH is frequently associated with small-cell lung cancer, it is extremely rare as the initial clinical feature in stage I small-cell lung cancer.

The Role of Thoracic Surgery in Small Cell Lung Cancer - A Large Longitudinal Analysis (2002-2015) Based on Real-World Data.

BACKGROUND: Most SCLC patients are diagnosed with extensive disease (ED) and the prognosis in this cohort remains poor. However, some patients are diagnosed with limited (LD) or very limited (VLD, T1-2, N0-1, M0) disease and previous data suggest that surgical resection might improve outcomes in these patients. Most of the existing evidence comes from small case series. For this reason, we investigated clinical features and surgical outcomes in a large cohort of resected SCLC patients. PATIENTS AND METHODS: We used a large pseudomized dataset (n = 32432) provided by the Munich Cancer Registry to analyze all documented SCLC patients (n = 5043) between 2002 and 2015. We correlated patients' characteristics as well as surgery modalities with survival data and describe trends in the role of surgery in SCLC over the time. RESULTS: We analyzed 5043 SCLC patients. A total of 161 (3.2%) received either oncological (lobectomy, bilobectomy and pneumonectomy) or limited resection (segmentectomy and wedge resection). We found a significant trend suggesting that resections in SCLC patients become less common in all stages of disease, accompanied by an increased proportion of oncological resections. This suggests a more accurate preoperative staging. In VLD resection was significantly associated with longer survival compared to nonsurgical management (log-rank P = .013). Survival was better with oncological resection compared to atypical resection. Administration of adjuvant chemotherapy was associated with better outcome in all resected patients (P = .01). CONCLUSION: VLD SCLC patients benefit from oncological resection. We recommend invasive staging in these patients to ensure VLD. Furthermore, adjuvant chemotherapy should be offered to all resected patients.

Consolidation nivolumab and ipilimumab versus observation in limited-disease small-cell lung cancer after chemo-radiotherapy - results from the randomised phase II ETOP/IFCT 4-12 STIMULI trial.

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR) = 1.02 (0.66-1.58), two-sided P = 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR = 0.95 (0.59-1.52), P = 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade ≥3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.

Survival after secondary liver resection in metastatic colorectal cancer: Comparing data of three prospective randomized European trials (LICC, CELIM, FIRE-3).

Metastatic colorectal cancer (mCRC) patients with liver-limited disease (LLD) have a chance of long-term survival and potential cure after hepatic metastasectomy. However, the appropriate postoperative treatment strategy is still controversial. The CELIM and FIRE-3 studies demonstrated that secondary hepatic resection significantly improved overall survival (OS). The objective of this analysis was to compare these favorable outcome data with recent results from the LICC trial investigating the antigen-specific cancer vaccine tecemotide (L-BLP25) as adjuvant therapy in mCRC patients with LLD after R0/R1 resection. Data from mCRC patients with LLD and secondary hepatic resection from each study were analyzed for efficacy outcomes based on patient characteristics, treatment and surveillance after surgery. In LICC, 40/121 (33%) patients, in CELIM 36/111 (32%) and in FIRE-3-LLD 29/133 (22%) patients were secondarily resected, respectively. Of those, 31 (77.5%) patients in LICC and all patients in CELIM were R0 resected. Median disease-free survival after resection was 8.9 months in LICC, 9.9 months in CELIM. Median OS in secondarily resected patients was 66.1 months in LICC, 53.9 months in CELIM and 56.2 months in FIRE-3-LLD. Median age was about 5 years less in LICC compared to CELIM and FIRE-3. Secondarily resected patients of LICC, CELIM and FIRE-3 showed an impressive median survival with a tendency for improved survival for patients in the LICC trial. A younger patient cohort but also more selective surgery, improved resection techniques, deep responses and a close surveillance program after surgery in the LICC trial may have had a positive impact on survival.

Patterns of Recurrence and Survival Rate After Complete Resection of Pathological Stage N2 Small-Cell Lung Cancer.

The benefits of surgical resection for patients with stage N2 limited-disease small-cell lung cancer (LD-SCLC) remain controversial. This retrospective study analyzed the survival and recurrence patterns of the patients diagnosed with pathological N2 (p-N2) LD-SCLC after radical resection. A total of 171 p-N2 LD-SCLC patients who underwent radical pulmonary resection and systematic lymphadenectomies at Shanghai Chest Hospital from July 2005 to June 2015 were enrolled. The influence of the mediastinal lymph node status (single or multiple nodes, single- or multiple-station) on the survival and recurrence patterns was retrospectively analyzed. The main recurrence sites were outside the chest cavity (54.8%) and hematogenous metastasis (67.4%). The bone and liver as initial recurrence sites had a poor prognosis, with a median overall survival (OS) of 13.100 months and 11.900 months, respectively. The median disease-free survival (DFS) of patients diagnosed with single and multiple p-N2 after surgery were 19.233 and 9.367 months (P = 0.001), and the median OS were 43.033 and 17.100 months (P < 0.001), respectively. In conclusion, recurrence occurred in the form of hematogenous metastasis mostly in the extra-thoracic part. Interestingly, patients diagnosed with single p-N2 benefited from radical resection. Surgery may be a treatment option regardless of the T stage if N2 SCLC with a single metastatic lymph node can be identified preoperatively.

Prognostic factors in patients with oligometastatic breast cancer - A systematic review.

AIM: Oligometastatic breast cancer (OMBC) is a disease-entity with potential for long-term remission in selected patients. Those with truly limited metastatic load (rather than occult widespread metastatic disease) may benefit from multimodality treatment including local ablative therapy of distant metastases. In this systematic review, we studied factors associated with long-term survival in patients with OMBC. METHODS: Eligible studies included patients with OMBC who received a combination of local and systemic therapy as multimodal approach and reported overall survival (OS) or progression-free survival (PFS), or both. The Quality in Prognosis Studies (QUIPS) tool was used to assess the quality of each included study. Independent prognostic factors for OS and/or PFS are summarized. RESULTS: Of 1271 screened abstracts, 317 papers were full-text screened and twenty studies were included. Eleven of twenty studies were classified as acceptable quality. Definition of OMBC varied between studies and mostly incorporated the number and/or location of metastases. The 5-year OS ranged between 30 and 79% and 5-year PFS ranged between 25 and 57%. Twelve studies evaluated prognostic factors for OS and/or PFS in multivariable models. A solitary metastasis, >24 months interval between primary tumor and OMBC, no or limited involved axillary lymph nodes at primary diagnosis, and hormone-receptor positivity were associated with better outcome. HER2-positivity was associated with worse outcome, but only few patients received anti-HER2 therapy. CONCLUSIONS: OMBC patients with a solitary distant metastasis and >24 months disease-free interval have the best OS and may be optimal candidates to consider a multidisciplinary approach.

Adjuvant MUC vaccination with tecemotide after resection of colorectal liver metastases: a randomized, double-blind, placebo-controlled, multicenter AIO phase II trial (LICC).

Resection of colorectal liver metastases (CRLM) is a potential curative treatment for patients with metastatic colorectal cancer (mCRC) with liver-limited disease (LLD). Although long-term survival improved considerably within the last decades, high recurrence rates of 50-75% after resection remain a major challenge.Tecemotide (L-BLP25) is an antigen-specific cancer vaccine inducing immunity against mucin-1 (MUC1). The LICC trial aimed to improve survival in patients with mCRC after R0/R1 resection of CRLM. LICC was a binational, randomized, double-blind, placebo-controlled, multicenter phase 2 study including patients with R0/R1 resected CRLM without evidence of metastatic disease outside the liver. Co-primary endpoints were recurrence-free survival (RFS) and 3-year overall survival (OS) rate, secondary endpoints were RFS and OS in subgroups with different MUC1 expression and safety. In total, 121 patients were 2:1 randomized between Oct 2011 and Dec 2014to receive tecemotide (N=79) or placebo (N=42). Baseline characteristics were well balanced. Median RFS was 6.1 months (95% CI 4.5-8.9) and 11.4 months (95% CI 3.7-21.2) (P = .1754), 3-year OS rate 69.1% and 79.1%, median OS 62.8 months and not reached in the tecemotide vs. placebo arm (P = .2141), respectively. Cox regression models revealed no dependence of RFS or OS on MUC1 expression. The most common tecemotide-related grade 3/4 adverse events were diarrhea, injection site reaction, intestinal perforation, peritonitis and tinnitus (1.3% each). The LICC trial failed to meet its primary endpoints of significantly improving RFS and OS with tecemotide. However, both arms showed unexpectedly long OS. MUC1 expression was not associated with outcome.EudraCT No: 2011-000218-20Clinical Trial Information: NCT01462513Financial Support: Merck KGaA, Darmstadt, Germany. Abbreviations: AE: adverse event; CP: cyclophosphamide; CRC: colorectal cancer; CT: computed tomography; ECOG: Eastern Cooperative Oncology Group; FU: follow-up; HR: hazard ratio; IHC: immunohistochemical staining; ITT: intention-to-treat; DSMB: Data Safety Monitoring Board; LLD: liver-limited disease; mCRC: metastatic colorectal cancer; MPLA: monophosphoryl lipid; AMRI: magnetic resonance imaging; MUC1: mucin 1; NA: not applicable; NCI-CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events; NS: normal saline; NSCLC: non-small-cell lung carcinoma; OS: overall surviva; lPP: per protocol; RAS: Rat sarcoma; RFS: recurrence-free survival; TEAE: treatment-emergent adverse event; UICC: Union for International Cancer Control; US: ultrasound; vs.: versus.

Once daily versus twice-daily radiotherapy in the management of limited disease small cell lung cancer - Decision criteria in routine practise.

BACKGROUND: In limited disease small cell lung cancer (LD-SCLC), the CONVERT trial has not demonstrated superiority of once-daily (QD) radiotherapy (66 Gy) over twice-daily (BID) radiotherapy (45 Gy). We explored the factors influencing the selection between QD and BID regimens. METHODS: Thirteen experienced European thoracic radiation oncologists as selected by the European Society for Therapeutic Radiation Oncology (ESTRO) were asked to describe their strategies in the management of LD-SCLC. Treatment strategies were subsequently converted into decision trees and analysed for agreement and discrepancies. RESULTS: Logistic reasons, patients' performance status and radiotherapy dose constraints were the three major decision criteria used by most experts in decision making. The use of QD and BID regimens was balanced among European experts, but there was a trend towards the BID regimen for fit patients able to travel twice a day to the radiotherapy site. CONCLUSION: BID and QD radiotherapy are both accepted regimens among experts and the decision is influenced by pragmatic factors such as availability of transportation.

Prognostic value of 18F-FDG PET/CT metabolic parameters in small cell lung cancer.

OBJECTIVE: To compare the prognostic values of metabolic parameters from pretreatment PET/CT between limited disease (LD) and extensive disease (ED) small cell lung cancer (SCLC) patients. METHODS: Data on 118 newly diagnosed SCLC patients (50 LD and 68 ED) who underwent pretreatment positron emission tomography-computed tomography (PET/CT) were reviewed. For PET, metabolic parameters were measured for: (1) primary tumor, maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis; and (2) all tumor lesions, SUVmax of the hottest tumor, whole body metabolic tumor volume (WBMTV), and whole body total lesion glycolysis (WBTLG). Prognostic values of metabolic parameters and other clinical variables were analyzed to predict overall survival (OS). RESULTS: In LD, SUVmax of the primary tumor was an independent prognostic factor for OS. Patients with high SUVmax showed significantly worse OS than those with low SUVmax. In ED, WBMTV and WBTLG were independent prognostic factors for OS. Patients with high WBMTV or WBTLG showed significantly worse OS than those with low WBMTV or WBTLG. CONCLUSIONS: SUVmax of primary tumor was the only independent prognostic factor for OS in LD SCLC patients. WBMTV and WBTLG were independent prognostic factors in ED SCLC patients.

Research progress on the correlation between herpangina and hand⁃foot⁃mouth disease / 口腔疾病防治

@# As acute enterovirus⁃induced infections, herpangina(HA) and hand⁃foot⁃mouth disease(HFMD) are simi⁃lar in many aspects. Although these diseases vary with time and region, many studies have shown that the viruses caus⁃ing HA and HFMD are consistent, and there is no notable difference in partial VP1 gene sequences between different vi⁃ruses. HA and HFMD also resemble each other in epidemiological features. Both infections show significant summer⁃time seasonality, have a strong connection with certain environmental conditions and are most prevalent in young chil⁃dren and infants. Herpangina is thought to be a mild disease, defined as vesicular enanthem and then ulcers of the fau⁃ces and soft palate with presentation of feve r, sore throat, and decreased appetite. HFMD, which could lead to severe symptoms, is also characterized by oral ulcers, although they are chiefly on the buccal mucosa and tongue, and typical vesicular rashes, which are most commonly found on the hands, feet, knees and buttocks. While HA is generally be⁃ lieved to be self⁃limited and has a favorable prognosis, HA with certain clinical characteristics, such as diarrhea, vomit⁃ing, limb jitter and sleepiness, can evolve into HFMD, according to some literature in recent years. However, HA is an independent risk factor for HFMD, and severe cases only present with herpes appearing at the isthmus of the fauces at an early stage, which indicates a strong correlation between them. Clinical manifestations of HA should be considered by medical staff to identify potential children with HFMD as early as possible to prevent its further development or transformation.

Clinical and molecular determinants of extrahepatic disease progression in patients with metastatic colorectal cancer with liver-limited metastases deemed initially unresectable.

BACKGROUND: No tools to predict the probability of extrahepatic disease progression (ePD) of initially unresectable, liver-limited metastatic colorectal cancer (mCRC) are currently available. To estimate the likelihood to develop ePD and to identify clinical and molecular factors that could predict extrahepatic progression-free survival (ePFS), we conducted an observational, retrospective, multicentre cohort study. METHODS: We retrospectively identified a cohort of 225 patients with initially unresectable liver-limited disease (LLD), treated from January 2004 to December 2017 with first-line doublets or triplet plus a biological agent at two Italian institutions. RESULTS: 173 (77%) patients experienced ePD which occurred within 1, 2 or 3 years from the diagnosis of mCRC in 15%, 49% and 66% of patients, respectively. Globally, 164 (73%) patients underwent a liver resection at some point of their disease history, and 54 (33%) of them underwent a subsequent locoregional treatment. Age > 70 years, locoregional nodal involvement at diagnosis of colorectal cancer and ≥4 liver metastases were significantly associated with higher risk of ePD while liver resections were associated with reduced risk of ePD. In the multivariable model, number of liver metastases (subdistribution HR, SHR 1.63, 95% CI 1.12 to 2.36; p = 0.01) and liver resections (SHR 0.43, 95% CI 0.29 to 0.63; p = 0.001) were still associated with ePD. Number of liver metastases < 4, no nodal involvement at diagnosis and liver resections were also associated with prolonged ePFS. CONCLUSIONS: The identified clinical factors could help physicians in personalising the intensity and aggressiveness of liver-directed treatments in patients with mCRC with initially unresectable LLD.

Effect of Pretreatment Platelet Parameters on Survival in Limited Disease Small Cell Lung Cancer.

Background: The aim of this study was to investigate the effect of platelet parameters before concurrent chemoradiotherapy (CCRT) on survival of patients with limited disease small cell lung cancer (LD-SCLC). Methods: This study consisted of patients who received CCRT due to LD-SCLC in the oncology clinic between 1997-2017. Examined platelet parameters included total platelet count (TPC), mean platelet volume, platelet distribution width, and platelet-lymphocyte ratio. The cut-off value for TPC was determined as 306x109/U (sensitivity: 62%, specificity: 75.5%), where patients below or equal to this level was classified as Group I, and those above as Group II. Results:The study included 90 patients whose mean age was 59 years (range: 42-83) and male ratio was 80.0% (n=72). Near three-fourths of patients (74.4%) were at clinical stage III. Among stage I-II patients, mOS was found as 126 months for Group I whereas it had not been reached in Group II (p=0.158). Stage III patients showed significantly lower mOS for Group 1 (16 [range: 14.1-17.8] months) compared to that in Group 2 (19.0 [range: 15.6-62.8] months; p=0.002). In multivariate analysis, Eastern Cooperative Oncology Group performance score (p=0.003), clinical stage (p<0.001), prophylactic cranial irradiation (p=0.004), and TPC (p=0.031) was determined as the most significant factors affecting survival. Conclusion: Our study suggests association of high baseline levels of TPC to improved survival in patients scheduled to undergo CCRT for LD-SCLC. Considering easiness and universal availability of TPC measurement, potential utilization of this biomarker may be promising to predict survival, albeit requiring validation by further well-designated prospective studies.