(18)FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response

To determine whether [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV fell from 12.6 (+/-6.3) to 8.1 (+/-2.9) after 1 week of chemoradiation (P=0.070). In nonresponders (72%), the results were 9.7 (+/-5.4) and 7.1 (+/-3.8), respectively (P=0.003). The MTV in responders fell from 36.6 (+/-22.7) to 22.3 (+/-10.4) cm(3) (P=0.180), while in nonresponders, this fell from 35.9 (+/-36.7) to 31.9 (+/-52.7) cm(3) (P=0.405). There were no significant differences between responders and nonresponders. The hypothesis that early repeat FDG-PET scanning may predict histomorphologic response was not proven. This may reflect an inflammatory effect of radiation that obscures tumour-specific metabolic changes at this time. This assessment may have limited application in predicting response to multimodal regimens for oesophageal cancer.     

Evaluation of thoracic tumors with 18F‐FMT and 18F‐FDG PET‐CT: A clinicopathological study

L‐[3‐¹⁸F]‐α‐methyltyrosine (¹⁸F‐FMT) is an aminoacid tracer for positron emission tomography (PET). The aim of this study was to determine whether PET‐CT with ¹⁸F‐FMT provides additional information for the preoperative diagnostic workup as compared with ¹⁸F‐FDG PET. PET‐CT studies with ¹⁸F‐FMT and ¹⁸F‐FDG were performed as a part of the preoperative workup in 36 patients with histologically confirmed bronchial carcinoma, 6 patients with benign lesions and a patient with atypical carcinoid. Expression of L‐type amino acid transporter 1 (LAT1), CD98, Ki‐67 labeling index, VEGF, CD31 and CD34 of the resected tumors were analyzed by immunohistochemical staining, and correlated with the uptake of PET tracers. For the detection of pulmonary malignant tumors, ¹⁸F‐FMT PET exhibited a sensitivity of 84% whereas the sensitivity for ¹⁸F‐FDG PET was 89% (p = 0.736). ¹⁸F‐FMT PET‐CT and ¹⁸F‐FDG PET‐CT agreed with pathological staging in 85 and 68%, respectively (p = 0.151). ¹⁸F‐FMT uptake was closely correlated with LAT1, CD98, cell proliferation and angiogenesis. The specificity of ¹⁸F‐FMT PET for diagnosing thoracic tumors was higher than that of ¹⁸F‐FDG PET. Our results suggest that coexpression of LAT1 and CD98 in addition to cell proliferation and angiogenesis is relavant for the progression and metastasis of lung cancer. © 2008 Wiley‐Liss, Inc.     

A nomogram that predicts pathologic complete response to neoadjuvant chemoradiation also predicts survival outcomes after definitive chemoradiation for esophageal cancer

Background

Pathologic complete response (pCR) to neoadjuvant chemoradiation for esophageal cancer is associated with improved outcomes. We evaluated whether a nomogram designed to predict who would have a pCR after trimodality therapy could also predict outcome after definitive chemoradiation.

Methods

Patients in this retrospective, single-institution analysis had received chemoradiation without surgery for esophageal cancer from 1998 through 2010; 333 such patients had complete information on all variables required for the pCR nomogram: sex; T status (by endoscopic sonography); tumor grade; tumor avidity on positron emission tomography (PET); and esophagogastroduodenoscopy (EGD)-directed biopsy results after chemoradiation. We used multivariate Cox regression to test potential associations between clinical outcomes [overall survival (OS), locoregional recurrence, and distant metastasis] and patient or treatment factors and the pCR nomogram score; the component variables of the nomogram were not reintroduced into the multivariate analysis.

Results

The median follow-up time for all patients (median age 66 years) was 18.2 months (30.7 months for those alive at the time of analysis). Patients with nomogram scores ≤125 (median for all patients) had significantly worse outcomes than patients with scores >125: median OS time 19.7 vs. 48.2 months; disease-free survival (DFS) time 6.1 vs. 31.1 months; locoregional failure-free survival time 17.7 months vs. not reached; and distant metastasis-free survival time 11.7 months vs. not reached (all P<0.001). Multivariate Cox regression analysis indicated that nomogram score independently predicted each survival outcome, along with other patient and disease factors.

Conclusions

The pCR nomogram score predicted survival outcomes in patients receiving definitive chemoradiation for esophageal cancer. Although this nomogram requires further validation, it may prove useful for stratifying patients for clinical trials designed to intensify treatments for patients at the highest risk of relapse.     

Influence of 18F‐fluorodeoxyglucose‐positron emission tomography on computed tomography‐based radiation treatment planning for oesophageal cancer

The addition of positron emission tomography (PET) information to CT‐based radiotherapy treatment planning has the potential to improve target volume definition through more accurate localization of the primary tumour and involved regional lymph nodes. This case report describes the first patient enrolled to a prospective study evaluating the effects of coregistered positron emission tomography/CT images on radiotherapy treatment planning for oesophageal cancer. The results show that if combined positron emission tomography/CT is used for radiotherapy treatment planning, there may be alterations to the delineation of tumour volumes when compared to CT alone. For this patient, a geographic miss of tumour would have occurred if CT data alone were used for radiotherapy planning.     

Pathologic complete response in breast cancer patients receiving anthracycline‐ and taxane‐based neoadjuvant chemotherapy

BACKGROUND:

The current study was conducted to evaluate the influence of race/ethnicity and tumor subtype in pathologic complete response (pCR) following treatment with neoadjuvant chemotherapy.

METHODS:

A total of 2074 patients diagnosed with breast cancer between 1994 and 2008 who were treated with neoadjuvant anthracycline‐ and taxane‐based chemotherapy were included. pCR was defined as no residual invasive cancer in the breast and axilla. The Kaplan‐Meier product‐limit was used to calculate survival outcomes. Cox proportional hazards models were fitted to determine the relationship of patient and tumor variables with outcome.

RESULTS:

The median patient age was 50 years; 14.6% of patients were black, were 15.2% Hispanic, 64.3% were white, and 5.9% were of other race. There were no differences in pCR rates among race/ethnicity (12.3% in black, 14.2% in Hispanics, 12.3% in whites, and 11.5% in others, P = .788). Lack of pCR, breast cancer subtype, grade 3 tumors, and lymphovascular invasion were associated with worse recurrence‐free survival (RFS) and overall survival (OS) (P ≤ .0001). Differences in RFS by race/ethnicity were noted in the patients with hormone receptor‐positive disease (P = .007). On multivariate analysis, Hispanics had improved RFS (hazard ratio [HR], 0.69; 95% confidence interval [95% CI], 0.49‐0.97) and OS (HR, 0.63; 95% CI, 0.41‐0.97); blacks had a trend toward worse outcomes (RFS: HR, 1.28 [95% CI, 0.97‐1.68] and OS: HR, 1.32 [95% CI, 0.97‐1.81]) when compared with whites.

CONCLUSIONS:

In this cohort of patients, race/ethnicity was not found to be significantly associated with pCR rates. On a multivariate analysis, improved outcomes were observed in Hispanics and a trend toward worse outcomes in black patients, when compared with white patients. Further research was needed to explore the potential differences in biology and outcomes. Cancer 2010. © 2010 American Cancer Society.     

Comparison of pathological complete response rates after neoadjuvant short-course radiotherapy or chemoradiation followed by delayed surgery in locally advanced rectal cancer

Introduction

Patients with locally advanced rectal cancer (LARC) who are unfit for chemoradiation (CRT), are often offered short-course radiotherapy followed by delayed surgery (SCRT-delay). This entails a lower radiation dose, no chemotherapy and a shorter treatment period. This may lower their chances for complete tumor response and, as such, organ-sparing approaches. The purpose of this study was to compare the pathological complete response (pCR) rates between neoadjuvant CRT and SCRT-delay in patients with LARC in a nationwide database from the Netherlands.

Clinical and pathological predictors of recurrence in breast cancer patients achieving pathological complete response to neoadjuvant chemotherapy

IntroductionDespite the excellent prognosis associated with pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), some patients still develop recurrence. Here, we investigated the outcomes of breast cancer patients with pCR, as well as the clinical and pathological predictors of cancer recurrence in these patients.Materials and methodsOf the 1599 breast cancer patients treated with NAC, we evaluated 394 patients who achieved pCR between January 2007 and December 2016. pCR was defined as no evidence of invasive cancer in breast. Residual in situ ductal and axillary lymph node diseases were not considered. We analyzed the outcomes using the Kaplan–Meier method. We assessed the association of clinical and pathological predictors with cancer recurrence using the cox proportional hazards regression model.ResultsThe median follow-up time was 63 months. The 5-year disease-free survival rate was 92.3%. Cancer recurrence was observed in 28 patients (7.1%): local recurrence 8 patients (2.0%), visceral metastasis 10 patients (2.5%), and brain metastasis 10 patients (2.5%). Brain metastases were found in patients with HER2 type breast cancer. The significant predictors of cancer recurrence were HER2 positivity (p = 0.04), clinical tumor size (p < 0.01), and lymph node metastasis (p < 0.01) before NAC on univariate analysis and only lymph node metastasis on multivariate analysis.ConclusionPatients achieving pCR to NAC showed excellent outcomes. Advanced clinical stage, large tumor size, presence of lymph node metastasis, and HER2 positivity before NAC were identified as significant predictors of cancer recurrence. Residual in situ ductal and lymph node diseases after NAC were not significant predictors.     

Total pathological complete response versus breast pathological complete response in clinical trials of reference and biosimilar trastuzumab in the neoadjuvant treatment of breast cancer

Introduction: Trastuzumab is a key drug in the neoadjuvant treatment of breast cancers that overexpress the human epidermal growth factor receptor 2 (HER2). Pathological complete response (pCR) is commonly used as an endpoint in neoadjuvant clinical trials of trastuzumab as evidence suggests it may be a surrogate for long-term survival. Several biosimilar candidates of originator or ‘reference’ trastuzumab are in development and have used pCR as a primary endpoint to assess therapeutic equivalence between treatments. The exact definition of pCR has varied across studies.

Areas covered: Here we look at the clinical relevance of pCR and compare rates of total pCR (defined as ypT0/is ypN0) and breast pCR (defined as ypT0/is) in clinical trials of reference and biosimilar trastuzumab.

Expert commentary: In order to evaluate the efficacy of neoadjuvant systemic therapies in a uniform way, standardization of trial endpoints is necessary. Future studies in HER2-positive breast cancer should include full assessment of the breast and lymph node basin before and after neoadjuvant systemic therapy, and the use of total pCR as the primary outcome.     

Rate and predictors of nodal pathological complete response following neoadjuvant endocrine treatment in clinically biopsy-proven node-positive breast cancer patients

BackgroundData on effectiveness and optimal use of neoadjuvant endocrine therapy (NET) in clinically biopsy-proven node-positive breast cancer is lacking. This study examined the incidence of axillary pathological complete response (pCR) on NET in clinically biopsy-proven node-positive breast cancer patients. Secondary, patient and tumour characteristics, as well as the optimal duration of NET in relation to the occurrence of axillary pCR were investigated.Material and methodsPatients diagnosed with primary hormone receptor positive, HER2 negative breast cancer between 2014 and 2019, with at least one positive axillary lymph node (pathologically proven), treated with NET were selected from the Netherlands Cancer Registry. The incidence of axillary pCR in combination with patient, tumour and treatment characteristics was analysed.ResultsIn a population of 561 patients, an axillary pCR of 7.3% on NET was observed. Median length of treatment was 8.1 months in the patients without vs. 8.8 months in those with axillary pCR, with no statistically significant difference. A p-value <0.30 was found for age, histologic type, clinical tumour status, hormone receptor status and the type of NET in univariable analysis. After multivariable logistic regression analyses, none of these variables were independently associated with the likelihood of an axillary pCR.ConclusionThe rate of axillary pCR after NET in HR + HER2-clinically biopsy-proven node-positive breast cancer patients is low. Factors independently associated with the likelihood of an axillary pCR could not be identified. More research is warranted regarding optimizing the duration of NET and the prognostic value of residual disease in the axilla after NET.     

18-fluorodeoxy-glucose positron emission computed tomography as predictive of response after chemoradiation in oesophageal cancer patients

IntroductionThe purpose of this study was to evaluate if a baseline, an interim or a post-chemoradiation (CTRT) 18-fluorodeoxy-glucose positron emission computed tomography (18F-FDG PET/CT) studies could provide information on pathologic response to CTRT and overall survival (OS).Materials and methodsThirty-one patients with histologically proven adenocarcinoma or squamous cell carcinoma of the oesophagus, fit for trimodality therapy were prospectively enrolled. Most were men (93.5%), and had a stage III cancer (74.2%). Chemotherapy consisted of oxaliplatin/5-fluorouracil (45.2%) and taxane/5-fluorouracil (54.8%). All patients underwent a baseline, an interim (performed 12 ± 2 days after the onset of CTRT) and a post-CTRT 18F-FDG PET/CT study. The 18F-FDG PET/CT variables evaluated were at baseline, interim and post-CTRT studies maximum standardised uptake value (SUVmax) and total lesion glycolysis (TLG). Clinical and 18F-FDG PET/CT parameters were correlated with pathologic complete response (pathCR) and OS.ResultsAmong the 31 patients studied, 61.3% achieved a clinical complete response (cCR) and 87.1% had surgery. The median OS was 35.1 months (95% confidence interval (CI): 19.9–NA). PathCR rate was 22.2%. There was only a marginal association between cCR and pathCR (p = 0.06). None of the other variables was predictive of pathCR. There was association between OS and baseline TLG (p = 0.03) at the optimal cutoff TLG value of 75.15. Additionally, TLG and ΔTLG post-CTRT were also associated with OS (p = 0.01 and 0.03, respectively).ConclusionNone of the PET parameters is predictive of pathCR but TLG at baseline and post-CTRT are prognostic of OS.     

基于机器学习预测乳腺癌患者新辅助化疗的病理完全反应

目的 基于乳腺癌电子病历系统收集的临床和病理特征数据构建机器学习模型,预测新辅助化疗(neoadjuvant chemotherapy,NAC)后的病理完全反应(pathological complete response,pCR).方法 回顾性收集2015年1月至2020年12月在本院接受NAC治疗和手术切除的乳腺癌...     

进展期胃癌新辅助治疗后病理完全缓解相关因素分析及风险预测模型建立

目的:探讨局部进展期胃癌新辅助治疗后病理完全缓解(pathological complete response,pCR)的临床相关因素。方法:回顾性分析2011年6月至2018年3月河北医科大学第四医院收治的452例局部进展期胃癌患者cT3～4N+～M0新辅助治疗及手术的临床资料,采用单因素分析及Logistic多因素回归分析法研究pCR的临床相关因素。结果:452例患者全部完成新辅助治疗及根治性手术,其中44例(9.7%)患者达到pCR。治疗前T分期为T3期、肿瘤最长径<4 cm、治疗前CA199≤30 U/mL、治疗结束与手术时间间隔≥6周、同步放化疗或联合靶向治疗方案与进展期胃癌新辅助治疗后高pCR率有关(均P<0.05)。治疗前T分期为T3期、CA199≤30 U/mL、肿瘤最长径<4 cm、新辅助同步放化疗或联合靶向治疗是影响进展期胃癌新辅助治疗后出现pCR的独立因素(均P<0.05)。以上每项指标出现pCR的预测评分均为1分。评分>2分患者出现pCR的概率为34.48%,评分≤2分患者出现pCR的概率为6.09%。结论:治疗前临床分期、CA19...     

The survival impact of delayed surgery and adjuvant chemotherapy on stage II/III rectal cancer with pathological complete response after neoadjuvant chemoradiation

Neoadjuvant concurrent chemoradiation (CCRT) is standard treatment for clinical stage II/III rectal cancers. However, whether patients with pathological complete response (pT0N0, pCR) should receive adjuvant chemotherapy and whether delayed surgery will influence the pCR rate remains controversial. A nationwide population study was conducted using the Taiwan Cancer Registry Database from January 2007 to December 2013. Kaplan‐Meier survival analysis was performed. Cox proportional hazards models were used to estimate multivariate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI). Of the 1,914 patients who received neoadjuvant CCRT, 259 (13.6%) achieved pCR and had better survival (adjusted HR: 0.37, 95% CI: 0.24‐0.58; p < 0.001). The cumulative rate of pCR rose up to 83.4% in the 9th week and slowly reached a plateau after the 11th week. Among the patients with pCR, those who received adjuvant chemotherapy had no survival benefits compared to those without adjuvant chemotherapy (adjusted HR: 0.72, 95 CI: 0.27–1.93; p = 0.52). By subgroup analysis, those younger than 70‐year old and received adjuvant chemotherapy had better survival benefit than those without adjuvant chemotherapy (adjusted HR: 0.19, 95% CI: 0.04–0.97; p = 0.046). Delayed surgery by 9–12 weeks after the end of neoadjuvant CCRT can maximize the pCR rate, which is correlated with better survival. Adjuvant chemotherapy may be considered in patients with pCR and aged <70‐year old, but further prospectively randomized controlled trials are warranted to validate these findings.