Partial pathologic response and nodal status as most significant prognostic factors for advanced rectal cancer treated with preoperative chemoradiotherapy

Background  

This study evaluated the impact of tumor regression grading (TRG) and other pathologic variates in a cohort of rectal carcinoma patients treated with neoadjuvant chemoradiotherapy (CRT). The value of a grading less than pCR for predicting survival is unknown. Tumor budding has not been systematically studied in rectal cancer after neoadjuvant therapy.     

Does the Value of PET-CT Extend Beyond Pretreatment Staging? An Analysis of Survival in Surgical Patients with Esophageal Cancer

Background  

Studies of positron emission tomography (PET) have focused mainly on tumor staging. The role of PET in predicting survival has received less attention. We sought to assess the relationship of pretreatment maximum standard uptake value (SUV_max) to survival in surgical patients with esophageal cancer.     

Early Assessment of Axillary Response with 18F-FDG PET/CT during Neoadjuvant Chemotherapy in Stage II–III Breast Cancer: Implications for Surgical Management of the Axilla

Background

If all initially node-positive patients undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC), overtreatment may occur in patients with complete response. Positron emission tomography–computed tomography (PET/CT) during NAC may predict axillary response and select patients appropriate for less invasive treatment after NAC. We evaluated the value of sequential ¹⁸F fluorodeoxyglucose (FDG) PET/CTs during NAC for axillary response monitoring in stage II–III breast cancer.

Methods

A total of 219 PET/CTs were performed in 80 patients with cytology-proven, node-positive disease at baseline (PET/CT1, n = 80) and twice during NAC (PET/CT2 n = 62, PET/CT3, n = 77). The relative changes in maximum standardized uptake value (SUV_max) of axillary nodes were examined for their ability to assess pathological response. All patients underwent ALND after chemotherapy, and complete axillary response (pCR), defined as absence of isolated tumor cells and of micro- and macrometastases, served as the reference standard.

Results

A total of 32 (40 %) patients experienced axillary pCR. The relative decrease in SUV_max was significantly higher in patients with pCR than in those without, both on PET/CT2 (p < 0.001) and PET/CT3 (p = 0.025). The area under the receiver operating characteristic curve values for PET/CT2 and PET/CT3 were 0.80 (95 % confidence interval 0.68–0.92) and 0.65 (95 % confidence interval 0.52–0.79), respectively. A relative decrease of ≥60 % on PET/CT2 had an excellent specificity (35 of 37, 95 %), a high positive predictive value (12 of 14, 86 %), and a sensitivity of 48 %—that is, it accurately identified histologic pCR in 12 of 25 patients with disease that responded to therapy.

Conclusions

¹⁸F-FDG PET/CT early during NAC is useful for axillary response monitoring in cytology-proven node-positive breast cancer because it identifies pathological response, thus permitting ALND to be spared.     

Bedeutung der PET für die Chirurgie des gastrointestinalen Stromatumors

Background

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the digestive tract. The GIST differ substantially from gastrointestinal carcinomas regarding tumor biology, treatment strategies and indications for surgery. Every surgeon involved in the treatment of GIST should be acquainted with these aspects.

Objectives

The aims of this article are to discuss the value of positron emission tomography (PET) in the surgical treatment of patients with GIST and to provide an outlook on the development of molecular tracers specifically tailored for GIST.

Results

PET is an invaluable decision aid in the multimodal therapy of GIST and particularly for deciding on surgical indications. Specific scenarios in which PET is used are primary staging monitoring during neoadjuvant therapy and staging and response assessment in the metastatic setting. The routinely used tracer is 18F-fluorodeoxyglucose (18F-FDG) and uptake reliably correlates with the metabolism of GIST lesions. Compared to computed tomography and magnetic resonance imaging (CT/MRI), 18F-FDG-PET often allows a more timely and accurate response assessment. GIST-specific molecular tracers, which could provide a direct prognosis regarding response and development of resistance to treatment, are currently in preclinical development. However, pharmacokinetic and immunological issues still need to be resolved. A distant aim is the development of “theranostics”, i.e. substances which serve both diagnostic and therapeutic purposes.

Discussion

PET has an established value in the multimodal treatment of GIST and is particularly useful for deciding on surgical indications.     

The Role of Preoperative [18F]Fluorodeoxyglucose Positron Emission Tomography in Predicting Early Recurrence After Curative Resection of Hepatocellular Carcinomas

Purpose  

¹⁸F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan reflects tumor differentiation and predicts clinical outcome in patients with hepatocellular carcinoma (HCC). We investigated the correlation of PET scans with tumor differentiation and early tumor recurrence (time-to-recurrence <1 year).     

Treatment Trends and Predictors of Adjuvant and Neoadjuvant Therapy for Gastric Adenocarcinoma in the United States

Purpose

Over the last decade, evidence suggesting the benefits of adjuvant therapy in the treatment of stage IB–III gastric adenocarcinoma has emerged, though the influence of these clinical trials and current treatment patterns is unknown. Our objectives were (1) to assess changes in gastric adenocarcinoma treatment over time, (2) to identify predictors of neoadjuvant or postoperative adjuvant therapy use, and (3) to identify factors associated with neoadjuvant therapy use.

Methods

Patients with stage IB–III gastric adenocarcinoma diagnosed between 1998 and 2007 in the National Cancer Data Base who underwent surgical resection were selected. Models were developed to identify factors associated with treatment.

Results

We identified 30,448 patients diagnosed with stage IB–III gastric adenocarcinoma who underwent surgical resection. Rates of systemic therapy receipt (either before or after surgery) increased by 71 % from 1998 to 2007 (p < 0.001). Receipt of neoadjuvant therapy receipt increased by 237 % over 10 years (p < 0.001), with the highest rate of increase seen at high-volume academic centers. American Joint Committee on Cancer (AJCC) stage and age were the strongest predictors of pre- or postoperative systemic therapy among surgical patients. Neoadjuvant therapy receipt was most strongly predicted by tumor location in the gastric cardia.

Conclusions

Treatment trends over the past decade reflect rapid adoption of evidence from randomized controlled trials by increased receipt of pre- and postoperative systemic therapy in the treatment of stage IB–III gastric adenocarcinoma. Although age and AJCC stage are strongly associated with receiving systemic adjuvant therapy, tumor location is the most significant predictor of neoadjuvant therapy.     

Accuracy of clinical examination, digital mammogram, ultrasound, and MRI in determining postneoadjuvant pathologic tumor response in operable breast cancer patients

Background  

To determine the accuracy, positive predictive value (PPV), and negative predictive value (NPV) of clinical examination and breast imaging techniques in determining pathologic complete response in patients with locally advanced breast cancer after neoadjuvant therapy.     

18F-FDG Uptake at Initial Staging of the Adrenocortical Cancers: A Diagnostic Tool but Not of Prognostic Value

Background

Adrenocortical carcinoma (ACC) is a rare cancer for which little level evidence exists to guide management. ¹⁸F-FDG PET (¹⁸F-fluorodeoxyglucose positron emission tomography) is an increasingly used diagnostic tool in patients with suspicious or indeterminate adrenal tumors. In some other solid tumors, ¹⁸F-FDG PET may offer prognostic information that can guide optimal patient treatment. The aim of the present study was to evaluate whether preoperative ¹⁸F-FDG PET based on SUVs assessments has a prognostic value in ACC patients.

Methods

A retrospective analysis was performed in patients who underwent ¹⁸F-FDG PET/CT for the evaluation of ACC. Inclusion criteria were an unequivocal diagnosis of ACC; all data from primary diagnosis available; ¹⁸F-FDG PET/CT performed prior to surgery or other treatment of the primary tumor; a minimum of 6-months follow-up for surviving patients. All ¹⁸F-FDG PET/CT procedures were reinterpreted in a blind fashion.

Results

Thirty-seven patients (23 without metastasis [M0], 14 with metastasis [M1]) fulfilled the study criteria. Median uptake values were tumor standardized uptake values (SUV)_max = 11 (range: 3–56) and a tumor/liver SUV_max ratio = 4.2 (range: 1.3–15). Median follow-up was 20 months. Although classic risk factors (tumoral stage, Weiss score) were associated with poor outcome, there was no correlation between primary tumor FDG uptake with overall survival (OS) and disease free survival (DFS) in M0 patients and with overall survival in M1 patients. ¹⁸F-FDG uptake correlated inconsistently with sinister histological features, such as atypical mitoses or necrosis.

Conclusions

At initial staging, primary tumor FDG uptake in ACC patients does not correlate with OS and DFS at 2 years. Patient prognosis and treatment strategy should not be based on uptake values.     

Impact of close surgical margin on local recurrence and survival in osteosarcoma

Purpose  

Whether neoadjuvant chemotherapy safely allows close margins in osteosarcoma patients is still unknown. This study investigates the impact of close margins on local recurrence (LR) and overall survival (OS) for osteosarcoma patients treated with neoadjuvant chemotherapy.     

Neoadjuvant LHRH analog plus estramustine phosphate combined with three-dimensional conformal radiotherapy for intermediate- to high-risk prostate cancer: a randomized study

Objective  

The objective of this study is to assess the safety and efficacy of a treatment regimen comprising neoadjuvant conventional androgen deprivation therapy (ADT) plus estramustine phosphate (EMP) combined with three-dimensional conformal radiotherapy (3D-CRT) for patients with intermediate- to high-risk prostate cancer.     

Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors (GIST): The EORTC STBSG Experience

Background

Preoperative imatinib therapy of locally advanced GIST may facilitate resection and decrease morbidity of the procedure.

Methods

We have pooled databases from 10 EORTC STBSG sarcoma centers and analyzed disease-free survival (DFS) and disease-specific survival (DSS) in 161 patients with locally advanced, nonmetastatic GISTs who received neoadjuvant imatinib. OS was calculated from start of imatinib therapy for locally advanced disease until death or last follow-up (FU) after resection of the GIST. DFS was calculated from date of resection to date of disease recurrence or last FU. Median FU time was 46 months.

Results

The primary tumor was located in the stomach (55 %), followed by rectum (20 %), duodenum (10 %), ileum/jejunum/other (11 %), and esophagus (3 %). The tumor resection after preoperative imatinib (median time on therapy, 40 weeks) was R0 in 83 %. Only two patients have demonstrated disease progression during neoadjuvant therapy. Five-year DSS/DFS rates were 95/65 %, respectively, median OS was 104 months, and median DFS was not reached. There were 56 % of patients who continued imatinib after resection. Thirty-seven GIST recurrences were diagnosed (only 5 local relapses). The most common mutations affected exon 11 KIT (65 %). Poorer DFS was related to primary tumor location in small bowel and lack of postoperative therapy with imatinib.

Conclusions

Our analysis comprising the largest group of GIST patients treated with neoadjuvant imatinib in routine practice indicates excellent long-term results of combined therapy in locally advanced GISTs.     

Diabetes Mellitus Affects Response to Neoadjuvant Chemoradiotherapy in the Management of Rectal Cancer

Introduction  

Although diabetic patients with rectal cancer have poorer outcomes than their nondiabetic counterparts, few studies have looked at diabetics’ response to therapy as an explanation for this disparity. This study compares the neoadjuvant chemoradiotherapy (CRT) response in diabetic and nondiabetic patients with locally advanced rectal cancers.     

Endoscopic Ultrasound Staging of Stenotic Esophageal Cancers May Be Unnecessary to Determine the Need for Neoadjuvant Therapy

Introduction

Endoscopic ultrasound (EUS) is an essential component of preoperative staging for esophageal cancer and is used to determine which patients should proceed to primary surgical resection or receive neoadjuvant therapy prior to surgery. However, when the EUS scope cannot traverse a tumor, the role of pre-dilatation is controversial due to the risk of perforation.

Methods

A retrospective review was conducted of all patients with esophageal tumor stenosis that could not accommodate the EUS scope who then proceeded with primary esophagectomy. The pathology results were classified based on the revised seventh edition American Joint Committee on Cancer staging system.

Results

A total of 27 patients met inclusion criteria. The majority of tumors were T3 (24/27, 89 %). There were no stage I tumors, 15 % (4/27) were stage II, 81 % (22/27) were stage III, and 4 % (1/27) were stage IV due to a resected solitary lung metastasis.

Conclusion

Tumors that cannot be assessed with an EUS scope due to tumor stenosis will have locally advanced disease in the majority of cases. In these situations, pre-dilatation of the tumor with EUS staging should be omitted when considering the risk of potential esophageal perforation and the patients should be referred for neoadjuvant therapy.     

Nutritional Support with Endoluminal Stenting During Neoadjuvant Therapy for Esophageal Malignancy

Background  

Perioperative nutrition remains a significant problem in patients undergoing neoadjuvant treatment for esophageal cancer. The aim of this study was to evaluate the effectiveness of esophageal stenting, feeding tube placement, or observation among esophageal cancer patients receiving neoadjuvant therapy.     

Prognostic Significance of Free Peritoneal Tumor Cells in the Peritoneal Cavity Before and After Neoadjuvant Chemotherapy in Patients with Gastric Carcinoma Undergoing Potentially Curative Resection

Background  

Free peritoneal tumor cells (FPTCs) are an independent prognostic factor in patients undergoing curative resection for gastric carcinoma. Whether neoadjuvant chemotherapy (NAC) can eliminate FPTCs in the peritoneal lavage remains unclear. The aim of the study was to determine the effect of NAC on FPTCs.     

Clinically Enlarged Lateral Pelvic Lymph Nodes Do Not Influence Prognosis after Neoadjuvant Therapy and TME in Stage III Rectal Cancer

Purpose  

The significance of lateral pelvic lymph nodes (LPLN) in rectal cancer remains unclear. The purpose of this study was to determine the outcome of patients with LPLNs identified on pretherapy imaging who were treated with neoadjuvant therapy followed by proctectomy without LPLN dissection.     

Major Reduction in Axillary Lymph Node Dissections After Neoadjuvant Systemic Therapy for Node-Positive Breast Cancer by combining PET/CT and the MARI Procedure

Background

Axillary lymph node dissection (ALND) is frequently performed for node-positive (cN+) breast cancer patients. Combining positron emission tomography/computed tomography (PET/CT) before-NST and the MARI (marking axillary lymph nodes with radioactive iodine seeds) procedure after neoadjuvant systemic therapy (NST) has the potential for avoiding unnecessary ALNDs. This report presents the results from implementation of this strategy.

Methods

All breast cancer patients treated with NST at the Netherlands Cancer Institute who underwent a PET/CT and the MARI procedure from July 2014 to July 2017 were included in the study. All the patients underwent tailored axillary treatment according to a protocol based on the combined results of PET/CT before NST and the MARI procedure after NST. With this protocol, patients showing one to three FDG-avid axillary lymph nodes (ALNs) on PET/CT (cN<4) and a tumor-negative MARI node receive no further axillary treatment. All cN (<4) patients with a tumor-positive MARI node receive locoregional radiotherapy, as well as patients with four or more FDG-avid ALNs [cN(4+)] and a tumor-negative MARI node after NST. An ALND is performed only for cN(4+) patients with a tumor-positive MARI node.

Results

The data of 159 patients who received a PET/CT before NST and a MARI procedure after NST were analyzed. Of these patients, 110 had one to three FDG-avid ALNs and 49 patients showed four or more FDG-avid ALNs on PET/CT before NST. For 130 patients (82%), ALND was omitted. Locoregional radiotherapy was administered to 91 patients (57%), and 39 patients (25%) received no further axillary treatment.

Conclusion

Combining pre-NST axillary staging with PET/CT and post-NST staging with the MARI procedure resulted in an 82% reduction of ALNDs for cN?+?breast cancer patients.

     

Prognostic Value of Metabolic Tumor Volume Measured by <Superscript>18</Superscript>F-Fluorodeoxyglucose Positron Emission Tomography in Patients with Esophageal Carcinoma

Purpose  

The aim of this study was to evaluate the prognostic value of metabolic tumor volume (MTV) measured by ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) in patients with esophageal carcinoma.     

Intraoperative lokale Tumorzelldissemination in der Rektumkarzinomchirurgie

Background

The influence of surgical principles and neoadjuvant therapy on the frequency of local tumor cell dissemination (LTCD) in rectal carcinoma surgery and its consequences for local recurrence and survival rates were analyzed.

Patients and methods

Data from the Erlangen registry for colorectal carcinomas (ERCRC) from 1969–2008 were compared with data from the literature published in 1980–2008.

Results

LTCD was observed in 6.7% in the ERCRC (n=2764) and a frequency of 6.9% was reported in in the literature (n=13,395). In the course of time and especially since the introduction of total mesorectal excision (TME) surgery, the incidence of LTCD has significantly decreased. Neoadjuvant treatment did not influence the frequency of LTCD. Following LTCD the rate of local recurrence significantly increased and the 5 year survival rate significantly decreased. This also applied to patients with neoadjuvant therapy.

Conclusions

Even in the era of TME surgery attention must to be paid to avoidance of LTCD. It is obligatory to document the occurrence of LTCD and it must be taken into consideration in routine quality assurance. In cases of LTCD postoperative chemoradiation is indicated for patients without neoadjuvant irradiation.     

Outcome of Microscopic Incomplete Resection (R1) of Colorectal Liver Metastases in the Era of Neoadjuvant Chemotherapy

Background  

Data from patients with colorectal liver metastases (CRLM) who received neoadjuvant chemotherapy before resection were reviewed and evaluated to see whether neoadjuvant chemotherapy influences the predictive outcome of R1 resections (margin is 0 mm) in patients with CRLM.