Survival among clinical stage I–III rectal cancer patients treated with different preoperative treatments: A population-based comparison

BackgroundRadical resection is regarded as the cornerstone of rectal cancer treatment. Preoperative (chemo)radiotherapy and adjuvant chemotherapy are often administered. This population-based study compares the survival in clinical stage I–III rectal cancer patients who received either preoperative radiotherapy, preoperative chemoradiotherapy or no preoperative therapy. As secondary research questions, the association of type of radical resection and adjuvant chemotherapy on survival is also investigated.MethodsPatients diagnosed between January 2006 and December 2011 with stage I–III rectal adenocarcinoma were retrieved from the Belgian Cancer Registry database. Multivariable Cox proportional hazards regression models were applied to evaluate the association of preoperative treatment, type of radical resection and use of adjuvant chemotherapy with survival, adjusting for the baseline characteristics age, gender, WHO performance status and clinical stage.ResultsA total of 5173 rectal cancer patients were identified. Preoperative treatment was as follows: none in 1354 (26.2%), radiotherapy in 797 (15.4%) and chemoradiotherapy in 3022 (58.4%) patients. The patient group who did not receive preoperative therapy or radiotherapy followed by radical resection had a lower observed survival compared to the patient group receiving preoperative chemoradiotherapy. The patient groups who underwent abdominoperineal excision and those receiving adjuvant chemotherapy had a worse observed survival compared to the patient group treated with sphincter-sparing surgery and no adjuvant therapy respectively. These effects were age-dependent. Multivariable analysis demonstrated similar findings for the observed survival conditional on surviving the first year since surgery.ConclusionIn this population-based study among clinical stage I–III rectal cancer patients treated with radical resection, a superior observed survival was noticed in the patient group receiving preoperative chemoradiotherapy compared to the patients groups receiving no or preoperative radiotherapy only, adjusting for case mix, type of radical resection and adjuvant chemotherapy. Additionally, higher adjusted observed survival was also detected for the patient groups with sphincter-sparing surgery or no adjuvant chemotherapy.     

High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC. A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

BackgroundThe optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined.AimTo compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC).MethodsRetrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014.Results47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. “not reached” (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS.ConclusionsCompared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.     

Stereotactic body radiation therapy for liver metastases: Clinical outcomes and literature review

Background and aimThe role of stereotactic body radiation therapy (SBRT) in the management of liver metastasis is increasing, using ablative doses with the goal of local control and ultimately improving survival. The aim of this study is to evaluate our initial results regarding local control, overall survival and toxicity in patients with liver metastases treated with this technique, due to the lack of evidence reported in Latin America.Materials/methodsWe performed a retrospective chart review from November 2012 to June 2018 of 24 patients with 32 liver metastases. Kaplan–Meier curves were constructed for local control and overall survival. Clinical and prognostic factors were further analyzed by independent analysis. Median follow-up period was 22 months (range, 1–65 months).ResultsMedian age was 62 years (range, 40–84 years). Colorectal carcinoma was the most common primary cancer. Overall 1-year and 2-years local control rates were 82% (95% Confidence Interval [CI], 70–98%) and 76.2% (95% CI, 45–90%), respectively. Median overall survival rate was 35 months (95%, CI 20.5–48 months). Overall 1-year and 2-year survival rates were 85.83% (95% CI, 64–99%) and 68% (95% CI, 45–84%), respectively. No acute or late grade 3 or 4 toxicity was observed during the follow-up period.ConclusionsSBRT achieves excellent local control and overall survival rates with low toxicity in patients with liver metastases. Based on our literature review, our results are consistent with larger reports. Further randomized trials are required to compare with other local therapies.     

Upregulation of IGF-1R Expression during Neoadjuvant Therapy Predicts Poor Outcome in Breast Cancer Patients

IntroductionThe insulin-like growth factor 1 receptor (IGF-1R) may be involved in the development of resistance against conventional cancer treatment. The aim of this study was to assess whether IGF-1R expression of breast tumors changes during neoadjuvant therapy and to study whether these changes were associated with survival.MethodsParaffin embedded tumor tissue was collected from pretreatment biopsies and surgical resections of 62 breast cancer patients who were treated with neoadjuvant chemotherapy or endocrine therapy. IGF-1R expression was determined immunohistochemically and compared before and after treatment.ResultsHigh membranous IGF-1R expression at diagnosis correlated significantly with ER positivity, low tumor stage (stage I/II) and longer overall survival (p < 0.05). After neoadjuvant treatment, membranous IGF-1R expression remained the same in 41 (65%) tumors, was upregulated in 11 (18%) tumors and downregulated in 11 (18%) tumors. Changes in membranous IGF-1R expression were associated with overall survival (log-rank test: p = 0.013, multivariate cox-regression: p = 0.086). Mean overall survival time for upregulation, no change, and downregulation in IGF-1R expression was 3.0 ± 0.5 years, 7.3 ± 1.0 years and 15.0 ± 1.8 years, respectively. Changes in other parameters were not significantly associated with survival.ConclusionNeoadjuvant therapy can induce changes in IGF-1R expression. Upregulation of IGF-1R expression after neoadjuvant treatment is a poor prognostic factor in breast cancer patients, providing a rationale for incorporating anti-IGF-1R drugs in the management of these patients.     

Prognostic factors for early relapse in non-metastatic triple negative breast cancer — real world data

BackgroundTriple negative breast cancer (TNBC) has the worst prognosis amongst all subtypes. Studies have shown that the achievement of pathologic complete response in the breast and axilla correlates with improved survival. The aim of this study was to identify clinical or pathological features of real-life TNBC patients with a higher risk of early relapse.Materials and methodsSingle-centre retrospective analysis of 127 women with TNBC, stage II–III, submitted to neoadjuvant treatment and surgery between January 2016 and 2020. Multivariate Cox regression analysis for disease free survival (DFS) at 2 years was performed and statistically significant variables were computed into a prognostic model for early relapse.ResultsAfter 29 months of median follow-up, 105 patients (82.7%) were alive and, in total, 38 patients (29.9%) experienced recurrence. The 2-year DFS was 73% (95% CI: 21.3–22.7). In multivariate analysis, being submitted to neoadjuvant radiotherapy [HR 2.8 (95% CI: 1.2–6.4), p = 0.017] and not achieving pathologic complete response [HR 0.3 (95% CI: 0.1–1.7), p = 0.011] were associated with higher risk of recurrence. In our prognostic model, the presence of at least one of these variables defined a subgroup of patients with a worse 2-year DFS than those without these features (59% vs. 90%, p < 0.001, respectively).ConclusionsIn this real-life non-metastatic TNBC cohort, neoadjuvant radiotherapy (performed due to insufficient clinical response to neoadjuvant chemotherapy or significant toxicity) impacted as an independent prognostic factor for relapse along with the absence of pathologic complete response identifying a subgroup of higher risk patients for early relapse that might merit a closer follow-up.     

A randomized clinical trial on the antitumoral effects of low molecular weight heparin in the treatment of esophageal cancer

The current treatment approaches for esophageal cancer are associated with poor survival, and there are ongoing efforts to find new and more effective therapeutic strategies. There are several reports on the antitumoral effects of low-molecular-weight heparins (LMWHs). We have assessed the possible survival benefit of LMWHs in esophageal malignancies. This was a randomized, single-blind, multicenter, Phase II clinical trial on nonmetastatic esophageal cancer candidate for neoadjuvant chemoradiotherapy. Patients were randomly assigned to the chemoradiotherapy-only arm or chemoradiotherapy plus enoxaparin arm using 1:1 allocation. Radiotherapy was delivered in 1.8-Gy daily fractions to a dose of 50.4 Gy in both groups. Paclitaxel 50 mg/m² and carboplatin (AUC 2) were administered weekly, concurrent with radiotherapy. In the intervention group, patients received enoxaparin (40 mg) and chemoradiation daily. 4–6 weeks after treatment, all patients underwent esophagectomy. After a median follow up of 7 months, estimated 1 year disease-free survival (DFS) in the intervention group was 78.9% and was 70% in the control groups ( p = 0.5). Toxicity from the experimental treatment was minimal, and there were no treatment-related deaths. A pathologically complete response in intervention and control group was 64.8% and 62.5%, respectively ( p = 0.9). There was a nonsignificant trend toward improved survival by the addition of enoxaparin to the concurrent chemoradiotherapy regimen. However, 1 y DFS of both groups were high as expected. A longer follow-up and a larger sample size are required.     

Postoperative radio-chemotherapy for rectal cancer: A retrospective analysis from a tertiary referral hospital

AimTo report results of postoperative radio-chemotherapy (RT-CHT) for rectal cancer (RC).BackgroundTotal mesorectal excision (TME) is an essential treatment method in rectal cancer (RC). Perioperative radiotherapy in locally advanced RC improves loco-regional free survival (LRFS). Preoperative radiotherapy is a preferred option; however, some patients are not referred for it. In case of the risk of loco-regional failure postoperative radio-chemotherapy (RT-CHT) is indicated.Material and methodsBetween 2004 and 2010, 182 patients with pathological stage II-III RC (TME performed — 41%, resection R0 — 88%, circumferential resection margin evaluated — 55.5% and was above 2 mm in 66% of them) received postoperative RT-CHT in our institution. Overall survival (OS) and LRFS were estimated with the Kaplan–Meier method. Univariate and multivariate analysis were performed to compare the impact of prognostic factors on survival.ResultsFive-year OS and LRFS rates were 63% and 85%, respectively. Loco-regional recurrence and isolated distant metastases rates were 11.5% and 19%, respectively. Multivariate analysis showed stage (III vs. II), HR: 2.3 (95% confidence interval [CI]: 1.4–3.8), p = 0.0001; extent of resection (R1−2 vs. R0), HR: 2.14 (95%CI: 1.14–3.99), p = 0.017, and age (>65 vs. ≤65 years), HR: 1.66 (95%CI: 1.06–2.61), p = 0.027 as prognostic factors for OS. Extent of resection (R1−2 vs. R0), HR: 3.65 (95%CI: 1.41–9.43), p = 0.008 had significant impact on LRFS.ConclusionDespite a suboptimal quality of surgery and pathological reports, the outcome in our series is close to that reported in the literature. We confirm a strong impact of the extent of resection on patient’s outcome, which confirms the pivotal role of surgery in the management of RC.     

Ⅰ期非小细胞肺癌组织血管内皮生长因子C、细胞角蛋白19表达与患者预后的相关性

目的:分析Ⅰ期非小细胞肺癌(NSCLC)组织血管内皮生长因子C(VEGF-C)、细胞角蛋白19(CK19)水平的变化,并探讨其与患者预后的相关性。方法:采用免疫组化检测肺癌组织中VEGF-C、CK19蛋白的表达,分析其与肺癌患者临床病理特点的相关性。随访至少3年,采用Kaplan-Meier法分析不同VEGF-C、CK19蛋白表达患者术后复发及疾病进展时间的差异。结果:VEGF-C和CK19在不同分化程度、胸膜侵犯患者肺癌组织中的表达比较差异均有统计学意义(P0.05)。VEGF-C表达与CK19表达呈显著正相关(r=0.483,P0.05)。术后3年,VEGF-C和CK19阳性患者复发率均显著高于VEGF-C和CK19阴性患者(x~2=14.16, 17.25,P0.05)。Kaplan-Meier法显示VEGF-C阳性、阴性者中位TTP分别为29.2个月(95%CI:27.5～30.9)、36.2个月(95%CI:35.0～37.5);CK19阳性、阴性者中位TTP分别为28.4个月(95%CI:26.6～30.2)、37.8个月(95%CI:36.4～39.1)。VEGF-C、CK19阴性者与阳性者的中位TTP比较差异有统计学意义(x~2=15.77、18.45,P0.05)。结论:I期NSCLC患者肺癌组织VEGF-C、CK19呈高表达,与术后局部复发密切相关,并可作为患者预后评估的参考指标。     

Multiple imputation to minimise bias from missing stage information in estimates of early cancer diagnosis in England: a population-based study

IntroductionMonitoring early diagnosis is a priority of cancer policy in England. Information on stage has not always been available for a large proportion of patients, however, which may bias temporal comparisons. We previously estimated that early-stage diagnosis of colorectal cancer rose from 32% to 44% during 2008–2013, using multiple imputation. Here we examine the underlying assumptions of multiple imputation for missing stage using the same dataset.MethodsIndividually-linked cancer registration, Hospital Episode Statistics (HES), and audit data were examined. Six imputation models including different interaction terms, post-diagnosis treatment, and survival information were assessed, and comparisons drawn with the a priori optimal model. Models were further tested by setting stage values to missing for some patients under one plausible mechanism, then comparing actual and imputed stage distributions for these patients. Finally, a pattern-mixture sensitivity analysis was conducted.ResultsData from 196,511 colorectal patients were analysed, with 39.2% missing stage. Inclusion of survival time increased the accuracy of imputation: the odds ratio for change in early-stage diagnosis during 2008–2013 was 1.7 (95% CI: 1.6, 1.7) with survival to 1 year included, compared to 1.9 (95% CI 1.9–2.0) with no survival information. Imputation estimates of stage were accurate in one plausible simulation. Pattern-mixture analyses indicated our previous analysis conclusions would only change materially if stage were misclassified for 20% of the patients who had it categorised as late.InterpretationMultiple imputation models can substantially reduce bias from missing stage, but data on patient’s one-year survival should be included for highest accuracy.     

Outcomes and treatment patterns as a function of time in stage IS testicular seminoma: A population-based analysis

ObjectivesTo assess outcomes and treatment patterns as a function of time in stage IS pure testicular seminoma patients using a population-based analysis.MethodsOne thousand one hundred and fifty-two stage I testicular seminoma patients with normal alpha-fetoprotein levels were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 1998 and 2005. Three hundred and twenty-three of these patients had persistent elevations of their serum lactate dehydrogenase (LDH) and/or beta subunit of human chorionic gonadotropin (bHCG) level post-orchiectomy, i.e., “stage IS” disease.ResultsMedian follow-up was 86 months. There was persistent elevation of LDH or bHCG levels post-orchiectomy in 19% and 15% stage I patients, respectively. Post-orchiectomy LDH and bHCG did not predict overall survival (OS) or cause-specific survival (CSS) in stage IS patients. There was a decrease in utilization of adjuvant RT in stage IS patients from 1998 (100%) to 2005 (58%, p = .01). The annual percentage decrease in RT utilization for stage IS patients was −5.4% (95% confidence interval: −7.7% to −3.9%). Modern, linear accelerator-based RT was associated with an improvement in OS. However, longer follow up is necessary to determine if the OS benefit persists.ConclusionsPost-orchiectomy LDH and bHCG did not predict OS or CSS in stage IS patients. There was a steady decrease in utilization of adjuvant RT in the United States in stage IS testicular seminoma patients between 1998 and 2005. This may be due to the increasing popularity of chemotherapy or active surveillance.     

Neoadjuvant oral vs. infusional chemoradiotherapy on locally advanced rectal cancer: Prognostic factors

Aim

To evaluate the prognostic factors and impact on survival of neoadjuvant oral and infusional chemoradiotherapy in patients with locally advanced rectal cancer.

Background

There is still no definitive consensus about the prognostic factors and the impact of neoadjuvant chemoradiotherapy on survival. Some studies have pointed to an improvement in overall survival (OS) and progression-free survival (PFS) in patients with tumor downstaging (TD) and nodal downstaging (ND).

Materials and methods

A set of 159 patients with LARC were treated preoperatively. Group A – 112 patients underwent concomitant oral chemoradiotherapy: capecitabine or UFT + folinic acid. Group B – 47 patients submitted to concomitant chemoradiation with 5-FU in continuous infusion. 63.6% of patients were submitted to adjuvant chemotherapy.

Results

Group A: pathologic complete response (pCR) – 18.7%; TD – 55.1%; ND – 76%; loco-regional response – 74.8%. Group B: pCR – 11.4%; TD – 50%; ND – 55.8%; LRR – 54.5%. The loco-regional control was 95.6%. There was no difference in survival between both groups. Those with loco-regional response had better PFS.

Conclusions

Tumor and nodal downstaging, loco-regional response and a normal CEA level turned out to be important prognostic factors in locally advanced rectal cancer. Nodal downstaging and loco-regional response were higher in Group A. Those with tumor downstaging and loco-regional response from Group A had better OS. Adjuvant chemotherapy had no impact on survival except in those patients with loco-regional response who achieved a higher PFS.     

Development of predictive models to identify advanced-stage cancer patients in a US healthcare claims database

BackgroundAlthough healthcare databases are a valuable source for real-world oncology data, cancer stage is often lacking. We developed predictive models using claims data to identify metastatic/advanced-stage patients with ovarian cancer, urothelial carcinoma, gastric adenocarcinoma, Merkel cell carcinoma (MCC), and non-small cell lung cancer (NSCLC).MethodsPatients with ≥1 diagnosis of a cancer of interest were identified in the HealthCore Integrated Research Database (HIRD), a United States (US) healthcare database (2010–2016). Data were linked to three US state cancer registries and the HealthCore Integrated Research Environment Oncology database to identify cancer stage. Predictive models were constructed to estimate the probability of metastatic/advanced stage. Predictors available in the HIRD were identified and coefficients estimated by Least Absolute Shrinkage and Selection Operator (LASSO) regression with cross-validation to control overfitting. Classification error rates and receiver operating characteristic curves were used to select probability thresholds for classifying patients as cases of metastatic/advanced cancer.ResultsWe used 2723 ovarian cancer, 6522 urothelial carcinoma, 1441 gastric adenocarcinoma, 109 MCC, and 12,373 NSCLC cases of early and metastatic/advanced cancer to develop predictive models. All models had high discrimination (C > 0.85). At thresholds selected for each model, PPVs were all >0.75: ovarian cancer = 0.95 (95% confidence interval [95% CI]: 0.94–0.96), urothelial carcinoma = 0.78 (95% CI: 0.70–0.86), gastric adenocarcinoma = 0.86 (95% CI: 0.83–0.88), MCC = 0.77 (95% CI 0.68–0.89), and NSCLC = 0.91 (95% CI 0.90 – 0.92).ConclusionPredictive modeling was used to identify five types of metastatic/advanced cancer in a healthcare claims database with greater accuracy than previous methods.     

CD20-specific chimeric antigen receptor-expressing T cells as salvage therapy in rituximab-refractory/relapsed B-cell non-Hodgkin lymphoma

Background aimsThe infusion of chimeric antigen receptor (CAR) T cells that target specific tumor-associated antigens is a promising strategy that has exhibited encouraging results in clinical trials. However, few studies have focused on the effectiveness and safety of CD20 CAR T cells in rituximab-refractory/relapsed (R/R) B-cell non-Hodgkin lymphoma (B-NHL) patients, particularly those treated with rituximab for a short time. This prospective study aimed to assess the effectiveness and toxicity of CD20 CAR T cells in R/R B-NHL patients previously treated with rituximab.MethodsThe authors conducted a prospective, single-center phase I study on the effectiveness and toxicity of CD20 CAR T cells in rituximab-treated R/R B-NHL patients (no. ChiCTR2000036350). A total of 15 patients with R/R B-NHL were enrolled between November 21, 2017, and December 1, 2021.ResultsAn overall response rate of 100% was shown in enrolled patients, with 12 (80%) achieving complete remission and three (20%) achieving partial remission for the best response. The median follow-up time was 12.4 months. Progression-free survival and overall survival were not yet reached by the data cutoff day. No patient developed grade 4 cytokine release syndrome, and only one patient had immune effector cell-associated neurotoxicity syndrome.ConclusionsAll enrolled B-NHL patients who were previously R/R to rituximab achieved different degrees of clinical response with tolerable toxicities. Notably, patients who had received rituximab within 3 months had a poorer prognosis.     

Retroperitoneal soft-tissue sarcomas: Radiotherapy experience from a tertiary cancer center and review of current evidence

BackgroundSurgery remains to be the main therapeutic approach for retroperitoneal sarcomas (RPS) although evidence supports that complementary radiotherapy increases local-control and survival. We present a multidisciplinary management and experience of a tertiary cancer center in the treatment of RPS and analyze current evidence of radiotherapy efficacy.Patients and methodsWe retrospectively reviewed 19 patients with primary or relapsed RPS treated between November 2009 and October 2018. Multidisciplinary approach comprised complete resection in 15 patients (79%) achieving resection R0 in 11 patients (58%), R1 in 4 patients (21%) and R2 in 2 patients (10%). Seven patients (37%) underwent a preoperative radiation (PRORT), 10 patients (53%), post-operative radiation (PORT) and 2 patients (10%), received radiotherapy exclusively. Ten patients (53%) received adjuvant chemotherapy.ResultsWith a median follow-up of 24 months (2–114 months), actuarial rates of loco-regional relapse free survival (LRFS) at 1, 2 and 3 years were 77%, 77% and 67%, respectively. Actuarial rates of distant-metastases-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) at 1, 2 and 3 years were 100%, 100% and 80% for DMFS; 94%, 77% and 67% for DFS and 100%, 91% and 91% for OS, respectively. Only surgical margins (negative vs. positive) showed significance for 3y-LRFS: 100% vs. 34.3%, p = 0.018. Treatment tolerance was acceptable with no acute or late toxicity higher than grade 2.ConclusionsComplementary radiotherapy appears to be useful and well tolerated for the multidisciplinary management of RPS. Presence of positive surgical margins seems to be the most relevant prognostic factor through the follow-up.     

EGFR突变与EML4-ALK融合共存的非小细胞肺癌的临床病理特征及治疗分析

目的:探讨表皮生长因子受体(EGFR)基因突变与棘皮动物微管相关样蛋白4与间变性淋巴瘤激酶(EML4-ALK)融合基因共存(以下简称双基因异常)的非小细胞肺癌的临床病理特征及治疗策略。方法:回顾性收集并分析2012年1月至2016年12月我院收治的EGFR突变与EML4-ALK融合基因共存的非小细胞肺癌患者的临床资料及病理特点。结果:11例双突变非小细胞肺癌占医院同期入院非小细胞肺癌患者的0.68%(11/1620);男性6例,女性5例;年龄23-70岁,平均年龄51.6岁;11例患者均不吸烟;腺癌9例,肉瘤样癌2例;临床分期,ⅠA期3例,ⅡB期1例,ⅢA期1例,ⅢB期1例,ⅠV期5例;6例行手术治疗,4例使用传统化疗,最好疗效为稳定(SD),最长无进展生存期(PFS)为6月;5例患者使用表皮生长因子酪氨酸激酶抑制剂(EGFR-TKⅠ)治疗,使用EGFR-TKⅠ最好疗效为部分缓解(PR),PFS为3-23月,中位PFS为9月;截止2017年12月,死亡4例,11例患者的生存时间为1-67月,中位存活时间为21月。结论:EGFR基因突变与EML4-ALK融合基因共存型非小细胞肺癌临床少见,多见于不吸烟或少吸烟的肺腺癌患者,双基因异常的非小细胞肺癌的靶向药物的治疗缺乏统一性,有待进一步研究,基于EGFR及EML4-ALK的磷酸化水平或肿瘤突变负荷选择靶向药物的个体化精准治疗是非常重要的。     

Trimodality treatment in malignant pleural mesothelioma – Ordeal or real deal?

BackgroundManagement of MPM is complex and controversial as there is a paucity of good quality evidence. We report the toxicity and outcomes in patients who received trimodality treatment for non-metastatic MPM at our institution.Methods & materialsWe reviewed the electronic medical records of surgically managed MPM patients at our institution in the last decade. Dosimetric parameters of target volume and organs at risk were documented by the treatment planning workstation. SPSS was used for statistical analysis.ResultsBetween January 2008 and October 2018, 21 patients underwent surgery for MPM – all but 2 patients underwent extra-pleural pneumonectomy (EPP); epithelioid MPM was the most common histology. All patients, except 2, received neoadjuvant Pemetrexed/platinum doublet chemotherapy. Fourteen patients received adjuvant hemithoracic RT; ten patients were treated with a conformal technique at our institute and dosimetric data was available for analysis. Average time to start RT after surgery was 51 days (range 32–82 days). All patients were treated with a conformal technique using IMRT/VMAT to a dose of 45Gy in 25 fractions. Mean overall RT duration was 35 days (range 30–42 days). Grade I/II Pneumonitis was seen in 4 patients. One patient developed grade III acute lung toxicity unrelated to RT. At a median follow up of 25 months, 8 patients had died, of whom six died due to the disease and two died in the immediate post op period. Two-year DFS and OS were 58% and 73%, respectively.ConclusionIn spite of the extensive surgery and complex hemithoracic RT, we demonstrated excellent dosimetry, toxicity profile and favorable outcomes in non-metastatic MPM.     

Dosimetric predictors of acute bone marrow toxicity in carcinoma cervix — experience from a tertiary cancer centre in India

BackgroundThe objective of this study was To determine the dose volume parameters predicting acute haematological toxicity in carcinoma cervix patients undergoing concurrent chemoradiotherapy.Materials and methodsAll patients that presented to the hospital between Jan 2019 and Dec 2019 were prospectively analyzed. Patients diagnosed to have Carcinoma Cervix and planned for concurrent chemoradiation by volumetric modulated arc therapy (VMAT) were included for analysis. Patients were assessed at baseline and every week during treatment for acute haematological toxicities. Dose volume parameters from treatment plans were correlated with RTOG grade of haematological toxicities.ResultsA total of 34 patients diagnosed to have squamous cell carcinoma of cervix were treated by radical radiotherapy by VMAT technique and concurrent chemotherapy. The most common stage of presentation was stage IIB (61.7%). 29 patients (85.2%) completed five cycles of weekly cisplatin. Statistical analysis for sensitivity and specificity of dosimetric parameters was performed using receiver operating characteristic (ROC) curve. The probability of developing bone marrow toxicity was analyzed using T test. Mean dose to bone marrow exceeding 28.5 Gy was significantly associated with bone marrow toxicity (sensitivity — 82.4%, specificity — 70.6%). On analyzing dose volume parameters, volume of bone marrow receiving 20 Gy, 30 Gy and 40 Gy (V20, V30 and V40) more than 71.75%, and 49.75% and 22.85%, respectively, was significantly associated with bone marrow toxicity.ConclusionsOur study concludes that mean dose to bone marrow exceeding 28.5 Gy has high sensitivity and specificity for predicting bone marrow toxicity in patients receiving IMRT. Volume of bone marrow receiving 20 Gy, 30 Gy and 40 Gy significantly correlated with acute haematological toxicity.     

Elevated CEA and CA19-9 serum levels independently predict advanced pancreatic cancer at diagnosis

Abstract

Purpose: It is suggested that tumour markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) could be used to predict the stage of pancreatic cancer. However, optimal cut-off values for CEA and CA19-9 are disputable. This study aimed to assess the value of CEA and CA19-9 serum levels at diagnosis of pancreatic ductal adenocarcinoma (PDAC) as predictors for the advanced stage of PDAC in patients discussed at pancreatic multidisciplinary team (MDT) meetings.

Methods: Patients with suspected PDAC discussed at MDT meetings from 2013 to 2017 were reviewed, in order to determine optimal cut-off values of both CEA and CA19-9.

Results: In total, 375 patients were included. Optimal cut-off values for predicting advanced PDAC were 7.0?ng/ml for CEA and 305.0?U/ml for CA19-9, resulting in positive predictive values of 83.3%, 73.6%, and 91.4% for CEA, CA19-9 and combined, respectively. Both tumour markers were independent predictors of advanced PDAC, demonstrated by an odds ratio of 4.21 (95% CI:1.85–9.56; p?=?0.001) for CEA and 2.58 for CA19-9 (95% CI:1.30–5.14; p?=?0.007).

Conclusions: CEA appears to be a more robust predictor of advanced PDAC than CA19-9. Implementing CEA and CA19-9 serum levels during MDT meetings as an additional tool for establishing tumour resectability is worthwhile for tailored diagnostics.     

Clinical significance of risk stratification of esophageal squamous cell carcinoma after neoadjuvant chemoradiation and surgery

ObjectiveNowadays, there were few studies reporting the risk stratification of patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiation (NCRT) and surgery. We aimed to establish a simple risk stratification to help postoperative detection and adjuvant treatment.MethodsWe included 146 patients with locally advanced ESCC who received NCRT followed by esophagectomy. The impacts of clinicopathological factors on overall survival (OS) and disease-free survival (DFS) were analyzed. The recurrence site, time, and frequency were recorded as well.ResultsThe median follow-up was 53 months. The pathological complete respond (pCR) group demonstrated better 5-year OS and DFS (78.6% and 77.0%) than the non-pCR group (44.8% and 35.2%, all P < 0.005). Multivariate analysis for the non-pCR group revealed perineural invasion (PNI) (HR:2.296, P = 0.013) and ypTNM stage (I/II vs III/IV) (HR:1.972, P = 0.046) were considered as independent unfavorable factors affecting OS, while PNI (HR:1.866, P = 0.045) and lymph vessel invasion (LVI) (HR:3.370, P < 0.001) were considered as independent adverse factors for DFS. Based on clinicopathological factors (including pCR, ypTNM stage, PNI, LVI), patients were divided into the low-risk (pCR), mediate-risk (non-pCR without PNI, LVI, stage III/IV), high-risk (non-pCR with one factor of PNI, LVI or stage III/IV (n = 45)), highest risk (non-pCR with two or more factors of PNI, LVI or stage III/IV) groups. The corresponding 5-year OS rates were 78.6%, 60.4%, 49.6%, 18.6%, respectively (P < 0.005) and 5-year DFS rates were 77.0%, 46.9%, 41.1%, 12.1%, respectively (P < 0.005). Adjuvant chemotherapy may improve survival in high or highest risk groups of patients with low prognostic nutritional index (< 49).ConclusionsA novel risk stratification based on clinicopathological factors may be conducive to postoperative surveillance and guide adjuvant chemotherapy.     

Pre-existing psychological disorders,diabetes, and pancreatic cancer: A population-based study of 38,952 Finns

BackgroundIt remains unclear how pre-existing depression, anxiety, and diabetes of different durations are associated with the risk of pancreatic cancer, its clinical characteristics, treatment modalities, and subsequent survival.MethodsFrom a register-based random sample of Finns residing in Finland at the end of the period 1987–2007, 6492 patients diagnosed with primary pancreatic cancer in 2000–2014, and 32 460 controls matched for birth cohort and sex, were identified. Pre-existing depression, anxiety, and diabetes were ascertained from the records of prescribed medication purchases. Information on pancreatic cancer outcomes was obtained from the Finnish cancer register. Data were analyzed using logistic and Cox regressions.ResultsThe risk of developing pancreatic cancer was found to be associated with long-term anxiety (treatment started 36 + months before the cancer diagnosis) (odds ratio (OR): 1.13, 95% confidence interval (95%CI): 1.04–1.22) and long-term diabetes (OR 1.72, 95%CI 1.55–1.90), as well as with new-onset (treatment started 0–24 months before the cancer diagnosis) depression (OR 1.59, 95%CI 1.34–1.88), anxiety (OR 1.76, 95%CI 1.50–2.07), and diabetes (OR 3.92, 95%CI 3.44–4.48). However, the effects of these new-onset conditions were driven by cases that began treatment within 3 months before the cancer diagnosis (concomitant period). Patients with long-term depression, anxiety and diabetes and those with new-onset anxiety had a higher risk of not receiving standard treatments. Lower survival was found for pancreatic cancer patients with new-onset depression (hazards ratio (HR) 1.38, 95%CI 1.16–1.64). Survival was not associated with pre-existing anxiety or diabetes.ConclusionsThe associations between pancreatic cancer risk and pre-existing depression and anxiety were mostly driven by concomitant effects. Individuals with diabetes, regardless of duration, should be closely monitored for pancreatic cancer. Pancreatic cancer patients with new-onset depression should be targeted to improve their survival.