Neoadjuvant Concurrent Radiotherapy Research Articles

Intra-Tumoral Pharmacokinetics of Pazopanib in Combination with Radiotherapy in Patients with Non-Metastatic Soft-Tissue Sarcoma.

Simple SummaryPazopanib plasma levels have been associated with treatment efficacy. Since pazopanib targets receptors present on cells in the vicinity of the tumor and on tumor cells themselves, measurement of pazopanib concentrations in tumor tissue might be an even better prognostic biomarker than plasma levels. The aim of our study was to quantify pazopanib concentrations in tumor tissue, correlate this with plasma concentrations, and assess whether this is a better biomarker for efficacy. A modest correlation was found between pazopanib tumor concentrations and plasma concentrations. Additionally, no correlation was found between pazopanib tumor concentrations and efficacy. We provide recommendations for future studies in which pazopanib concentrations are measured.There is a lack of understanding whether plasma levels of anticancer drugs (such as pazopanib) correlate with intra-tumoral levels and whether the plasma compartment is the best surrogate for pharmacokinetic and pharmacodynamic evaluation. Therefore, we aimed to quantify pazopanib concentrations in tumor tissue, to assess the correlation between tumor concentrations and plasma concentrations and between tumor concentrations and efficacy. In this clinical trial, non-metastatic STS patients were treated with neo-adjuvant concurrent radiotherapy and pazopanib. Plasma samples and tumor biopsies were collected, and pazopanib concentrations were measured using liquid chromatography-tandem mass spectrometry. Twenty-four evaluable patients were included. The median pazopanib tumor concentration was 19.2 µg/g (range 0.149–200 µg/g). A modest correlation was found between tumor concentrations and plasma levels of pazopanib (ρ = 0.41, p = 0.049). No correlation was found between tumor concentrations and percentage of viable tumor cells (p > 0.05); however, a trend towards less viable tumor cells in patients with high pazopanib concentrations in tumor tissue was observed in a categorical analysis. Possible explanations for the lack of correlation might be heterogeneity of the tumors and timing of the biopsy procedure.

Neoadjuvant Concurrent Radiotherapy and Chemotherapy in Early Breast Cancer Patients: Long-Term Results of a Prospective Phase II Trial.

Simple SummaryThe originality of this prospective study is to use radiation therapy in association with chemotherapy before surgery and permit patients to preserve their breasts or to undergo immediate reconstruction. This neoadjuvant strategy can therefore allow one-stage breast reconstructive surgery, the so-called “reverse technique”.Background: Neoadjuvant concurrent radiochemotherapy makes it possible to increase the breast conservation rate. This study reports the long term outcome of this treatment. Methods: From 2001 to 2003, 59 women with T2–3 N0–2 M0 invasive breast cancer (BC) not amenable to upfront breast conserving treatment (BCS) were included in this prospective, non-randomized phase II study. Chemotherapy (CT) consisted of four cycles of continuous 5-FU infusion and Vinorelbine. Starting concurrently with the second CT cycle, normofractionated RT was delivered to the breast and LN. Breast surgery was then performed. Results: Median follow-up (FU) was 13 years [3–18]. BCS was performed in 41 (69%) patients and mastectomy in 18 patients, with pathological complete response rate of 27%. Overall and distant-disease free survivals rates at 13 years were 70.9% [95% CI 59.6–84.2] and 71.5% [95% CI 60.5–84.5] respectively. Loco regional and local controls rates were 83.4% [95% CI 73.2–95.0] and 92.1% [95% CI 83.7–100], respectively. Late toxicity (CTCAE-V3) was assessed in 51 patients (86%) with a median follow-up of 13 years. Fifteen presented grade 2 fibrosis (29.4%), 8 (15.7%) had telangiectasia, and 1 had radiodermatitis. Conclusions: This combined treatment provided high long-term local control rates with limited side-effects.

Neoadjuvant chemoradiotherapy combined with surgery in the treatment of potentially operable thoracic squamous cell carcinoma of the esophagus(ChiCTR-OIC-17011648): A phase II single center clinical study.

e15543 Background: To investigate the efficacy and safety of neoadjuvant radiotherapy and chemotherapy combined with surgery in the treatment of potentially operable thoracic esophageal squamous cell carcinoma. Methods: Nineteen patients with advanced thoracic esophageal squamous cell carcinoma hospitalized in our hospital from July 2016 to June 2018 were prospectively studied. All patients received neoadjuvant concurrent radiotherapy and chemotherapy: intensity modulated conformal radiotherapy (40 ∽ 44Gy/20 ∽22f, 2 Gy/f), chemotherapy (paclitaxel 150 ∽ 175 mg/m2 d1, 22+lobaplatin 25-30 mg/m2 d2, 23, 2 cycles). After radiotherapy and chemotherapy, the efficacy and safety of the operation were observed. Results: Two case (10.5%) was completely remitted after neoadjuvant radiotherapy and chemotherapy, 17 cases (89.5%) were partially remitted, and the objective effective rate was 100%. All patients underwent radical surgery successfully, the R0 resection rate was 100% and the pCR rate was 52.6%. The main adverse reactions of neoadjuvant radiotherapy and chemotherapy were granulocytopenia and grade III-IV granulocytopenia. The rate of survival was 16.7%, and anastomotic leakage occurred in 1 patients after operation. Conclusions: Neoadjuvant chemoradiotherapy for thoracic esophageal squamous cell carcinoma can effectively reduce the volume of the tumor, significantly reduce the pathological grade, improve the resection rate, and have less adverse reactions, which is worthy of clinical application. Clinical trial information: ChiCTR-OIC-17011648.

Neoadjuvant chemoradiotherapy for esophageal/gastroesophageal carcinoma.

Esophageal/gastroesophageal junction (GEJ) adenocarcinoma is increasingly treated with trimodality therapy. We present our experience using carboplatin/paclitaxel and radiotherapy followed by surgery. Consecutive patients with distal esophageal/GEJ adenocarcinoma (≥T2 or N+) treated from July 2010 to October 2011 were identified. Treatment included neoadjuvant carboplatin/paclitaxel with concurrent radiotherapy (CRT) to 50.4 Gy using an IMRT technique and then Ivor Lewis esophagogastrectomy (ILE). PET/CT was performed prior to and after CRT. Patient/treatment characteristics and tumor response were analyzed. Over this timeframe, 16 patients completed trimodality therapy. All were male, median age of 60 years (45-72 years). All tumors were grade 2-3 with mean tumor length of 4.4 cm (1-9 cm). A median of 6 cycles (5-9 cycles) neoadjuvant carboplatin/paclitaxel were administered. Average time from diagnosis to CRT completion was 76 days (44-141 days) and 60 days (35-92 days) from CRT end to surgery. Neoadjuvant CRT was well tolerated with mean weight loss of 3.9 kg. All pts had R0 resections. No anastomotic leaks or perioperative mortality occurred. Mean hospital stay was 13 days (8-28 days). Pathologic complete response (pCR) was seen in 38% of patients, microscopic residual disease (isolated tumor cells or <2 mm) in 31%, and macroscopic residual disease remained in 31%. Mean SUV reduction was 41% (0-100%). Of 11 patients with ≥35% SUV decrease, 45% had pCR and 27% had microscopic residual disease. Three patients had signet ring features. Of these, 2 had no SUV reduction and all had gross residual disease, including the only patient with positive nodal disease. Trimodality therapy utilizing concurrent carboplatin/paclitaxel and radiotherapy to 50.4 Gy followed by surgery was well tolerated and resulted in significant pathologic complete response or minimal residual disease. Further investigation of predictive factors for response is needed to best tailor therapy in the management of esophageal/GEJ adenocarcinoma.

Neoadjuvant carboplatin/paclitaxel with concurrent radiotherapy followed by surgery for esophageal/gastroesophageal junction adenocarcinoma: A single-institution experience.

e14712 Background: Esophageal and gastroesophageal junction (GEJ) adenocarcinoma is increasingly treated with trimodality therapy. We present our experience using carboplatin/paclitaxel and radiotherapy followed by surgery. Methods: Consecutive patients with distal esophageal/GEJ adenocarcinoma (≥T2 or N+) treated from July 2010 to October 2011 were identified. All patients received neoadjuvant carboplatin/paclitaxel with concurrent radiotherapy (CRT) to 50.4 Gy using an IMRT technique and then Ivor Lewis esophagogastrectomy. PET/CT was performed prior to and after CRT. Patient/treatment characteristics and tumor response were analyzed. Results: Over this timeframe,17 patients completed trimodality therapy using this regimen. All were male with a median age of 59 years (45-72). All tumors were grade 2-3 adenocarcinoma with mean tumor length of 4.4 cm (1-9). A median of 6 cycles (5-9) neoadjuvant carboplatin/paclitaxel were administered, 3 patients received additional adjuvant therapy. Average time from diagnosis to CRT completion was 78 days (44-141) and from CRT end to surgery was 62 days (35-92). Neoadjuvant CRT was well tolerated with mean weight loss of 3.5 kg. All pts had R0 resections. No anastomotic leaks or perioperative mortality occurred. Mean hospital stay was 13.6 days (8-28). Pathologic complete response (pCR) was seen in 41% of patients, microscopic residual disease (isolated tumor cells or &lt;2mm) in 29%, and macroscopic residual disease remained in 29%. Mean SUV reduction was 41% (0-100). Of 12 patients with ≥35% SUV decrease, 50% had pCR and 25% had microscopic residual disease. Three patients had signet ring features; of these 2 had no SUV reduction and all had gross residual disease, including the only patient with pN disease. Conclusions: Trimodality therapyutilizing carboplatin/paclitaxel and CRT to 50.4 Gy IMRT followed by Ivor Lewis esophagogastrectomy was well tolerated and resulted in significant pathologic complete response or minimal residual disease. Further investigation of predictive factors for response is needed to best tailor therapy in the management of esophageal/GEJ adenocarcinoma.

Incidence of therapy-related leukemia following chemoradiotherapy for esophageal cancer

e15663 Background: The combination of chemotherapy and concurrent radiotherapy (CRT) has recognized as a curative alternative for several stage of esophageal cancer. On the other hands, a sufficiently long survival time has increased treatment-related late toxicities. However, the frequency and the pathogenesis of secondary malignancies that is the most serious late-onset complication are still unclear. Methods: From July 2000 to March 2008, 348 patients with esophageal squamous cell carcinoma underwent CRT. All patients received chemotherapy consisting with nedaplatin (80 mg/m2, div day1) and fluorouracil (700 mg/m2, ci day 1–5) and concurrent long T field irradiation (2 Gy daily, up to 30 Gy). A hundred patients received a single course as the neoadjuvant setting. Two cycles of CRT as the definitive or palliative setting were administered in 248 patients. Median and average follow-up durations are 8 and 21 months (1 to 92), respectively. Results: Four patients, who achieved CR after CRT, developed leukemia. Case1, 60-yo-male, developed overt acute myeloid leukemia (AML) from myelodysplastic syndrome 48 months after CRT. Cytogenetic analysis showed complicated abnormalities including deletion 5q. Case2, 64-yo-male, developed AML M0 with t(9;22)(q34;q11) 44 months after CRT. Case3, 72-yo-male, developed Burkitt leukemia with t(8;14)(q24;q32) 19 months after CRT. Case4, 65-yo-male, developed myeloid crisis of chronic myelogenous leukemia with complicated abnormalities including t(9;22)(q34;q11) 48 months after CRT. Case 1 and 3 had localized disease and received single course of neoadjuvant CRT. Case 2 and 4 had advance disease and received 2 courses of CRT. All patients eventually died of leukemia. Conclusions: Since platinum and fluorouracil have shown relatively low chance of secondary neoplasm, our data demonstrates that the concurrent radiotherapy which involves massive bone marrow tissue may increase the risk of leukomogenesis. To this end, atypical cytogenetic abnormalities seen in the present cases give a new insight into the biology of therapy-related leukemia. Notably, this is the first report presenting the incidence of secondary leukemia by nedaplatin. No significant financial relationships to disclose.