Neoadjuvant Chemoradiation Therapy Followed by Extrafascial Hysterectomy in Locally Advanced Type II Endometrial Cancer Clinically Extending to Cervix

PurposeThe role of neoadjuvant chemoradiation therapy in locally advanced type II endometrial cancer is controversial. We thus aimed to present our experience with the hypothesis that neoadjuvant chemoradiation therapy is associated with similarly high rates of downstaging and locoregional control for type II endometrial cancer and type I endometrial cancer.Methods and MaterialsThirty-four patients with type II endometrial cancer with clinical evidence of cervical ± parametrium involvement treated with neoadjuvant external beam radiation therapy (45-50.4 Gy in 25-28 fractions) and high-dose-rate brachytherapy with a median total dose of 20 Gy (range, 15-27.5) in 4 fractions (range, 3-5) and concurrent platinum chemotherapy ± adjuvant chemotherapy from 2008 to 2018 were retrospectively reviewed. Patients with type I pathologic diagnoses and those treated with definitive (rather than preoperative) intent were excluded.ResultsPathologic characteristics were as follows: 38% were carcinosarcoma, 18% serous, and 24% clear cell. Ninety-four percent of patients were downstaged to an extrafascial hysterectomy, and 94% had negative surgical margins. The 2-year local control, regional control, distant control, disease-free survival, and overall survival were 87.8%, 81.3%, 76.3%, 52.5%, and 63.7%, respectively. There was 1 subacute grade 3 and 1 late grade 3 small bowel obstruction, directly attributable to radiation therapy.ConclusionsNeoadjuvant chemoradiation therapy effectively downstages the majority of locally advanced type II endometrial cancers, thereby increasing the likelihood of achieving complete resection with negative margins.     

Rôle de l’irradiation ganglionnaire chez les patientes indemnes d’envahissement ganglionnaire après chimiothérapie néoadjuvante pour un cancer du sein : expérience du centre René-Huguenin

PurposeNeoadjuvant chemotherapy generally induces significant changes in the pathological extent of disease. This potential down-staging challenges the standard indications of adjuvant radiation therapy. We assessed the utility of lymph node irradiation in breast cancer patients with pathological N0 status (pN0) after neoadjuvant chemotherapy and breast-conserving surgery.Patients and materialsAmong 1054 breast cancer patients treated with neoadjuvant chemotherapy in our institution between 1990 and 2004, 248 patients with clinical N0 or N1-N2 lymph node status at diagnosis had pN0 status after neoadjuvant chemotherapy and breast-conserving surgery. Cox regression analysis was used to identify factors influencing locoregional recurrence-free survival, disease-free survival and overall survival.ResultsAll 248 patients received breast irradiation, and 158 patients (63.7%) also received lymph node irradiation. With a median follow-up of 88 months, the 5-year locoregional recurrence-free survival and overall survival rates were respectively 89.4% and 88.7% with lymph node irradiation and 86.2% and 92% without lymph node irradiation (no significant difference). Survival was poorer among patients who did not have a pathological complete primary tumor response (pCR) (hazards ratio [HR] = 3.05; 95% CI, 1.17 to 7.99) and in patients with N1-N2 clinical status at diagnosis ([HR] = 2.24; 95% CI, 1.15 to 4.36). Lymph node irradiation did not significantly affect survival.ConclusionsRelative to combined breast and local lymph node irradiation, isolated breast irradiation does not appear to be associated with a higher risk of locoregional relapse or death among breast cancer patients with pN0 status after neoadjuvant chemotherapy. These results need to be confirmed in a prospective study.     

Establishing and validating predictive nomograms for lateral pelvic lymph node metastasis in patients with rectal cancer based on radiologic factors and clinicopathologic characteristics

IntroductionIt is critical to accurately predict the occurrence of lateral pelvic lymph node (LPN) metastasis. Currently, verified predictive tools are unavailable. This study aims to establish nomograms for predicting LPN metastasis in patients with rectal cancer who received or did not receive neoadjuvant chemoradiotherapy (nCRT).Materials and methodsWe carried out a retrospective study of patients with rectal cancer and clinical LPN metastasis who underwent total mesorectal excision (TME) and LPN dissection (LPND) from January 2012 to December 2019 at 3 institutions. We collected and evaluated their clinicopathologic and radiologic features, and constructed nomograms based on the multivariable logistic regression models.ResultsA total of 472 eligible patients were enrolled into the non-nCRT cohort (n = 312) and the nCRT cohort (n = 160). We established nomograms using variables from the multivariable logistic regression models in both cohorts. In the non-nCRT cohort, the variables included LPN short diameter, cT stage, cN stage, histologic grade, and malignant features, and the C-index was 0.930 in the training cohort and 0.913 in the validation cohort. In the nCRT cohort, the variables included post-nCRT LPN short diameter, ycT stage, ycN stage, histologic grade, and post-nCRT malignant features, and the C-index was 0.836 in the training dataset and 0.827 in the validation dataset. The nomograms in both cohorts were moderately calibrated and well-validated.ConclusionsWe established nomograms for patients with rectal cancer that accurately predict LPN metastasis. The performance of the nomograms in both cohorts was high and well-validated.     

Controversies in locoregional management of breast cancer with low volume pN0(i+) and pN1mi nodal disease

ABSTRACT

Introduction: The pathologic status of the axillary lymph nodes is an important prognostic factor in patients with breast cancer. With the transition from axillary lymph node dissection (ALND) to sentinel lymph node biopsy (SLNB) for patients with clinically node negative breast cancer, there has been an increase in detection of pN0(i+) breast cancer with isolated tumor cells and pN1mi disease with micrometastatic nodal involvement. The prognostic impact of small volume nodal involvement and the role of locoregional radiotherapy, especially in the era of modern systemic therapy, are unclear.

Areas covered: This review examines contemporary data evaluating the prognostic impact of pN0(i+) and pN1mi breast cancer on locoregional recurrence and survival outcomes, then discusses controversies related to the use of adjuvant locoregional radiation therapy in the presence of low volume nodal disease. Relevant papers were identified by searching multiple engines for articles published since 2000.

Expert opinion: Sentinel lymph node biopsy without completion ALND is a standard surgical option for patients with pN0(i+) and pN1mi disease. The available evidence does not support routine use of adjuvant locoregional radiation therapy in patients with pN0i+ or pN1mi disease, but locoregional radiotherapy should be considered in the presence of concomitant high-risk features and patient factors.     

Trimodality Therapy With or Without Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer

BackgroundBladder-sparing chemoradiation therapy is a definitive first-line treatment option for muscle-invasive bladder cancer. Randomized trials have demonstrated that the addition of neoadjuvant chemotherapy to radical cystectomy or radiation monotherapy results in a survival benefit. Whether neoadjuvant chemotherapy improves outcomes when used with definitive chemoradiation is unknown.Patients and MethodsWe identified 2566 patients in the National Cancer Data Base with cT2-4N0M0 urothelial cell carcinoma of the bladder treated with definitive intent concurrent chemoradiation from 2004 to 2015. The exposure of interest was receipt of neoadjuvant chemotherapy versus those without neoadjuvant chemotherapy. The primary outcome was overall survival defined from the time of diagnosis. Kaplan–Meier and multivariable Cox proportional hazard analyses were used to compare survival between groups. Sensitivity analyses tested (1) an interaction term for clinical T stage and (2) defining survival from start of radiation (as opposed to time of diagnosis) to address potential leading time bias.ResultsWe identified 462 patients treated with neoadjuvant chemotherapy followed by chemoradiation and 2104 patients treated with chemoradiation alone. With a median follow-up of 6.2 years, we found no difference in survival between groups: 5-year or 10-year overall survival of 30.6% (95% confidence interval [CI], 28.4%-32.9%) in the neoadjuvant group versus 31.8% (95% CI, 27.0%-36.8%) in the standard chemoradiation therapy group and 13.3% (95% CI, 11.2%-15.5%) in the neoadjuvant group versus 13.0% (95% CI, 8.4%-18.7%) in the standard chemoradiation therapy group, respectively (log-rank P = .19). On multivariable analysis we found no association between receipt of neoadjuvant chemotherapy and overall survival (hazard ratio, 1.01; 95% CI, 0.88-1.15; P = .921). The sensitivity analyses did not identify any differential effect by clinical T stage nor by defining survival from start of radiation.ConclusionThese results do not support the routine addition of neoadjuvant chemotherapy to definitive chemoradiation for bladder cancer, and optimizing the chemotherapy sequencing and regimens for bladder-preserving approaches to muscle invasive bladder cancer should continue to be studied under prospective clinical trials.     

Postoperative Radiotherapy for Patients With Completely Resected Pathologic N2 Non–Small-Cell Lung Cancer: A Retrospective Analysis

BackgroundAdjuvant radiotherapy in non–small-cell lung cancer (NSCLC) is still controversial. The purpose of this retrospective study was to evaluate the role of postoperative radiotherapy (PORT) in terms of local control and survival in pathologic N2 NSCLC.Patients and MethodsFrom January 2003 to December 2008, 66 patients with pathologic N2 NSCLC received PORT. Mediastinal lymph node metastases were classified into single (12 patients) or multiple (54 patients) stations. All patients received conformal radiation therapy, with a median total dose of 50.4 Gy. Target volumes included the bronchial stump, ipsilateral hilum, all pathologically involved lymph node regions, and all the lymph nodes between 2 noncontiguous pathologic nodal stations. The pattern of failure was considered as locoregional or systemic, or a combination of both. Locoregional failure was defined as in field or out of field.ResultsMedian follow-up time was 34.9 months (range 3.5-62.8 months). Local control was 80% at 12 months, 77.2% at both 24 and 36 months, and 72.1% at 60 months. The pattern of failure was locoregional in 3 patients (1 out of field and 2 in field) and systemic in 25 patients, with 12 patients presenting both locoregional and distant disease. Overall survival at 12, 36, and 60 months was 77%, 44%, and 37%, respectively. Median survival time was 34 months. The number of pathologically involved lymph node stations was a prognostic factor for local control (P = .05), cancer-specific survival (CSS) (P = .04), and disease-free survival (DFS) (P = .04).ConclusionDespite the limitations of the present study, mainly represented by its retrospective nature, our data support the role of PORT in terms of locoregional control and overall survival benefit; the number of involved mediastinal lymph nodes represents a significant prognostic factor in patients with pathologic N2 NSCLC.     

The Importance of Postoperative Radiation Therapy in Multimodality Management of Locally Advanced Breast Cancer: A Phase II Trial of Neoadjuvant MVAC,Surgery, and Radiation

Purpose: To determine the impact of postoperative radiation on locoregional relapse and overall survival rate in a multimodality protocol for locally advanced breast cancer (LABC).Material and Methods: Of the patients entered in the protocol, 55 were evaluable. Treatment consisted of: neoadjuvant MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) until a maximum response had been achieved; modified radical mastectomy; 6 courses of postoperative adjuvant MVAC chemotherapy, and chest wall irradiation (CWXRT). Multivariate analysis of locoregional response and overall survival was done.Results: Of the total, 42 patients received chest wall radiation; 28 of these also received radiation to regional lymph nodes. Chest wall doses ranged from 45 Gy to 50.4 Gy to the whole chest wall, with 31 patients receiving an additional chest-wall boost. The incidence of locoregional relapse with and without radiation was 7% vs. 31%, respectively (p = 0.026). An overall survival benefit was seen in those receiving radiation, with a mean overall survival of 50 months vs. 20 months, and a 3-year overall survival of 88% vs. 46% with and without radiation, respectively (p = 0.003). Multivariate analysis showed that overall survival was affected by the presence of pathological CR (p = .047), the number of pre-operative chemotherapy cycles (p = .036) and whether or not they received radiation (p = 0.003). Neither the interval between surgery and radiation, technique of radiation, nor radiation modality significantly affected local control.Conclusion: The significant improvement in local regional control and overall survival with the addition of radiation suggests that radiation should be an integral part of multimodality management of locally advanced breast cancer.     

Lymph node yield after rectal resection in patients treated with neoadjuvant radiation for rectal cancer: A systematic review and meta-analysis

BackgroundThe lymph node status represents a major prognostic factor in colorectal cancer. However, it was demonstrated that neoadjuvant chemoradiotherapy (CRT) decreases the numbers of lymph nodes in the specimen. Several studies describe less than 12 lymph nodes in the resected specimen of rectal cancer patients after neoadjuvant radiation. This meta-analysis quantifies the influence of neoadjuvant CRT or radiotherapy (RT) only on the lymph node yield in rectal cancer patients.MethodsWe performed a systematic review and searched PubMed, EMBASE and the Cochrane Library without any language restriction from 1st of January 1980 until 31st March 2015. Two reviewers examined all publications independently and extracted the relevant data if the study assessed lymph node counts or positive lymph node yields of patients who received neoadjuvant treatment compared with patients who did not receive neoadjuvant treatment. Meta-analyses were conducted to quantify the mean difference in lymph node yield.ResultsA total of 34 articles (including 37 datasets) were included in the meta-analyses. Neoadjuvant CRT resulted in a mean reduction of 3.9 lymph nodes (95% confidence interval [CI] 3.7–4.1) and an average reduction in harvested positive lymph nodes of 0.7 (95% CI 0.2–1.2) compared with patients who received no neoadjuvant therapy. Individuals who received neoadjuvant RT had, in average, 2.1 lymph node less (95% CI 1.7–2.5) resected compared with their counterparts who received no neoadjuvant treatment.ConclusionsNeoadjuvant CRT or RT only in rectal cancer patients leads to a decrease in lymph node harvest of approximately four and two lymph nodes, respectively. We therefore stress the importance of intensifying all efforts from involved subspecialities (i.e. surgeons and pathologists) to reach the benchmark harvest of 12 resected lymph nodes according to current guidelines.     

Résultats à long terme de la chimioradiothérapie néoadjuvante des cancers de l’œsophage : étude rétrospective monocentrique sur 102 patients

Purpose and objectivesTo report survival and morbidity of a large homogeneous cohort of patients with a locally advanced esophageal or cardia carcinoma and put in evidence predictive factors of locoregional control and survival.Patients and methodsHundred and two patients were treated at the university hospital of Tours between 1990 and 2010 and received neo-adjuvant chemoradiation therapy with external irradiation (40 Gy–44 Gy) and two courses of chemotherapy (5-fluoro-uracile and cisplatine). Esophagectomy associated with lymph node dissection was performed about ten weeks after the end of chemoradiation therapy.ResultsThe median follow-up was 22.4 months [6–185 months]. The overall survival rates at 2 and 5 years were 53% and 27%, respectively. The median overall survival was estimated at 27 months. The overall 2-year survival between patients “responders” and patients “non-responders” was 67% vs 26%, respectively (P < 0.0001). In case of histological response, there was a benefit in terms of overall survival (P < 0.0001), locoregional control (P < 0.0036) and disease-free survival (P < 0.001). Overall survival at 2 years was 64% for ypN0 group vs 32% for ypN1 group (P < 0.0001). The median survival was estimated at 37 months against 15 months in the absence of lymph node involvement (P < 0.0001).ConclusionOur results in terms of survival, tolerance and morbidity and mortality were comparable to those in the literature. Complete histological response of lymph node was associated with an improvement of local control, disease-free survival and overall survival.     

Lymph node yield in rectal cancer surgery: Effect of preoperative chemoradiotherapy

Aim

Adequate lymph node resection in rectal cancer is important for staging and local control. This study aims to verify the effect of neoadjuvant chemoradiation, as well as some clinicopathological features, on the yield of lymph nodes in rectal carcinoma.

Methods

Data on consecutive patients who had total mesorectal excision for rectal adenocarcinoma at a single cancer center between January 2003 and July 2008 were reviewed. No patient had any prior pelvic surgery or radiotherapy. Patients had neoadjuvant chemoradiotherapy if they were stage II or III.

Results

A total of 116 patients were included. The mean age was 53 years (range 29–83). Fifty-nine patients (51%) received neoadjuvant therapy before resection. The mean number of lymph nodes removed was 18 (range 4–67) per specimen. There was less lymph node yield in patients who received neoadjuvant therapy (16 vs. 19, p = 0.008). Only 64% of patients who had preoperative therapy had 12 lymph nodes or more in the specimen as opposed to 88% of those who had surgery upfront (p = 0.003). Other factors associated with lower lymph node yield included: female sex (p = 0.03) and tumour location in the lower rectum (p = 0.002). Age, tumour stage and grade, type of operation and surgical delay did not affect the number of lymph nodes removed.

Conclusion

Preoperative chemoradiotherapy for rectal cancer results in reduction in lymph node yield. Female sex and lower rectal tumours are also associated with retrieval of fewer lymph nodes.     

Outcomes of rectal cancer with liver oligometastases

Purpose

In patients with oligometastatic colorectal cancer to the liver, long term survival is possible and a multi-modality treatment approach may be considered. This is a report of a single institution experience of oligometastatic rectal cancer patients after treatment of the primary tumor and pelvic lymph nodes with extended course chemoradiation therapy.

Methods

Between 2004 and 2013, 26 oligometastatic rectal cancer patients with liver metastases were treated with extended course chemoradiation at our institution followed by total mesorectal excision (TME). Amongst these there were 17 men and 9 women. The mean age at the time of diagnosis was 59.8 years, with a range from 36 to 87 years of age. Eleven patients had metastases in other sites in addition to liver, and one patient in our cohort had lung metastasis with no liver metastasis. Kaplan-Meier method was used to generate overall survival (OS), progression free survival (PFS), distant metastases (DM) and local control (LC).

Results

OS rates were 95%, and 70% at 12 and 24 months respectively, with a mean survival time of 40.5 months. PFS rates were 91% and 36% at 12 and 24 months respectively, with a mean PFS time of 23.1 months. LC rates were 91% and 66% at 12 and 24 months respectively. DM rates were 0% and 61% at 12 and 24 months respectively. Finally, when censoring deaths, progression of liver metastases and distant progression, Kaplan-Meier analysis demonstrated five events of local failure.

Conclusions

This series demonstrated an OS of 70% at 24 months, with a mean survival of 40.5 months. Significantly, LC was only 66% despite the use of extended course chemoradiation and TME. This data suggests that many patients with oligometastatic rectal cancer will survive past 2 years, and that a substantial number will fail locally as well as distantly. Therefore, a multimodality approach is reasonable. Recent data suggests that a hypofractionated radiation regiment of 25 Gy in 5 Gy fractions allows an equivalent LC compared to extended course chemoradiation with 50.4 Gy in 1.8 Gy fractions. A short course of radiation may be more consistent with the goals of care of the oligometastatic rectal cancer patient who is at high risk of recurrence.     

Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial

The results of the PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy regarding overall survival, disease-free survival, and recurrence rates after preoperative (chemo)radiotherapy and TME surgery in yp stage II and III rectal cancer patients.BackgroundThe discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision (TME).Patients and methodsThe PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1:1) to observation or adjuvant chemotherapy after preoperative (chemo)radiotherapy and TME. Radiotherapy consisted of 5 × 5 Gy. Chemoradiotherapy consisted of 25 × 1.8–2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival.ResultsOf 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62–1.39;P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60–1.07;P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39).ConclusionThe PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo)radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual.Registration numberDutch Colorectal Cancer group, CKTO 2003-16, ISRCTN36266738.     

Have the changes in treatment of rectal cancer made a significant difference to our patients?

The treatment for patients with locally advanced, resectable rectal cancer has evolved over the years. Various combinations and sequences of chemotherapy, radiation therapy, and total mesorectal excision (TME)-based surgery are the mainstay of current therapy. Preoperative combined chemoradiation, followed by surgery, is now the preferred treatment strategy, with the majority of patients receiving either infusion fluorouracil (5-FU) or capecitabine (Xeloda) with radiation. Clinical trials with oxaliplatin (Eloxatin)-based neoadjuvant chemoradiation have not shown improvement in the pathologic complete response rate (pCR) compared with 5-FU; however, final data addressing local recurrence rates and disease-free survival are pending.The use of adjuvant chemotherapy following preoperative chemoradiation and surgery has not been optimally defined. Some studies have shown that patients who obtained significant pathologic downstaging after chemoradiation and surgery have improved survival with the use of adjuvant chemotherapy. Since FOLFOX (folinic acid, 5-FU, and oxaliplatin) is the preferred adjuvant chemotherapy regimen for stage III colon cancer based on randomized clinical trial results, FOLFOX is also recommended for rectal cancer patients as an adjuvant therapy approach.     

Neoadjuvant Chemotherapy in Locally Advanced Cervical Carcinoma – a Role in Patients with Para-aortic Lymph Node Involvement? A 10-year Institutional Experience

AimsOverall survival and progression-free survival with concomitant chemoradiotherapy for locally advanced cervical carcinoma have been described as 66% and 58%, respectively, at 5 years. Para-aortic lymph node involvement significantly increases the risk of relapse and death. The role of additional chemotherapy in these patients is as yet undefined. This aim of the present study was to determine the outcome of a cohort of para-aortic lymph node-positive patients treated with neoadjuvant chemotherapy followed by extended-field chemoradiation compared with patients treated with extended-field chemoradiation without neoadjuvant chemotherapy.Materials and methodsWe reviewed patients with International Federation of Gynaecology and Obstetrics (FIGO) 2014 stage IB1–IVA cervical carcinoma who received extended-field radiotherapy in addition to standard pelvic chemoradiotherapy with or without neoadjuvant chemotherapy, at University College London Hospital (January 2007 to January 2018). Patients in open clinical trials were excluded.ResultsOverall, 47 patients (15.8% of 298 eligible patients) with pelvic and/or para-aortic lymph node-positive cervical carcinoma received extended-field radiotherapy. Nineteen patients (40.4%) had both neoadjuvant chemotherapy (all received six cycles) and extended-field radiotherapy (median 44 days); 28 (59.6%) patients received extended-field radiotherapy alone (median 43 days). All patients completed radical radiotherapy within 49 days. We observed evidence that patients receiving neoadjuvant chemotherapy and extended-field radiotherapy had a lower risk of death (median follow-up 4.8 years, three deaths) compared with extended-field radiotherapy alone (median follow-up 3.0 years, 11 deaths; hazard ratio = 0.27, 95% confidence interval 0.08–1.00; P = 0.05). Three-year overall survival rates were 83.3% (95% confidence interval 66.1–100) and 64.6% (95% confidence interval 44.6–84.6), respectively. A PFS benefit was seen (hazard ratio 0.25, 95% confidence interval 0.08–0.77; P = 0.02), with 3-year PFS rates of 77.8% (95% confidence interval 58.6–97.0) and 35.0% (95% confidence interval 14.0–56.0), respectively.ConclusionsOur institutional experience suggests that the use of additional systemic therapy before chemoradiotherapy benefits patients with locoregionally advanced (FIGO 2018 IIIC2) cervical cancer. Neoadjuvant chemotherapy was associated with longer overall survival and PFS, without compromising definitive extended-field chemoradiation.     

Patterns of regional failure in stage III non-small cell lung cancer treated with neoadjuvant chemoradiation therapy and resection

PurposeTreatment of locally advanced non-small cell lung cancer (LA-NSCLC) involves definitive chemoradiation therapy (CRT) or neoadjuvant CRT and resection, but radiation treatment volumes remain in question. With CRT, involved-field radiation therapy (IFRT) is replacing elective nodal irradiation, reducing toxicity, and allowing dose escalation. However, prior reports of IFRT describe failures only after radical CRT; with improved local control after resection, IFRT may lead to more regional recurrences. Our objective is to evaluate pattern-of-failure in patients with LA-NSCLC treated with split-course IFRT, chemotherapy, and subsequent surgery.Methods and MaterialsPatients treated between December 2004 and 2010 were included. Imaging scans demonstrating failure were fused into the radiation therapy planning computed tomography, and recurrent nodes were contoured to determine pattern-of-failure (involved versus elective nodal failure [INF vs ENF]). Locoregional progression-free survival and distant metastasis-free survival were calculated using Kaplan-Meier methodology. The cumulative incidence of regional recurrence (CIRR) was determined with death as a competing risk.ResultsForty-five patients met inclusion criteria, and patients with RR had a lower rate of pN0 than those without RR (20% vs 60%, P = .02). With a median follow-up of 2.9 years, median survival was not reached, and 3-year locoregional progression-free survival and distant metastasis-free survival were 53% and 35%, respectively. Two and 3-year CIRR were 25% and 33%, respectively. There were no local failures. Thirteen (29%) patients had RR, 8 with INF only and 5 with ENF alone or both, totaling 27 recurrences. Only 2 (4%) ENF occurred without INF, both with distant metastasis, and no elective node was the first and only site of failure.ConclusionsOur data suggest that IFRT does not compromise regional control in the neoadjuvant management of LA-NSCLC. Tailoring nodal volumes may improve treatment-related morbidity and allow for dose intensification of involved nodes. Further research is necessary to improve regional and distant control.     

Intraoperative presacral electron boost following preoperative chemoradiation in T3-4Nx rectal cancer: initial local effects and clinical outcome analysis.

BACKGROUND AND PURPOSE: To analyze early results of a single institution experience using adjuvant intraoperative electron radiation therapy (IOERT) presacral boost in locally advanced rectal cancer following preoperative chemoradiation.Materials and methods: In a 63 month period (March 1995-June 2000), 100 consecutive T(3-4)N(x) rectal cancer patients were treated with preoperative chemoradiation (45-50 Gy plus oral Tegafur or 5-Fluorouracil continuous intravenous infusion), radical surgery and IOERT presacral boost (mean dose, 12.5 Gy; range, 10-15 Gy). Adjuvant chemotherapy (5-FU-leucovorin: 4-6 cycles) was given to 52 patients. The median age was 63 years, and 39 patients were >or=70 years old (65 males). Clinical staging was performed with computed tomography (94%) and/or endorectal ultrasound (71%) categorizing 90 cT(3), 10 cT(4), 20 cN(x), and 36 cN(+). Abdomino-perineal resection was performed in 41 cases. RESULTS: The IOERT cancellation rate was 6%. With a median follow-up of 23 months in IOERT treated patients, three developed pelvic recurrence: one anastomotic and one in the posterior vaginal wall (simultaneously with distant metastatic disease); and one presacral (in-field IOERT) as the only site of initial failure. Distant metastasis has been observed in 14 patients (exceptionally in pT(0-1) downstaged patients: 1/20; 5%). Overall treatment tolerances, including neoadjuvant and surgical segments, were acceptable. The actuarial 4-year estimations of local control, disease-free and overall survival are 94, 75 and 65%, respectively. CONCLUSIONS: IOERT electron boost to the presacral region is feasible to integrate systematically in the intensive combined treatment of locally advanced rectal cancer, including neoadjuvant chemoradiation segment. Topography of pelvic recurrences identified 2/3 relapses located in non-IOERT boosted anatomic intrapelvic sites: posterior vaginal wall and anastomotic suture. Presacral recurrence in locally advanced rectal cancer seems to be of low incidence, in a non-subspecialized academic surgical practice coordinated with a multidisciplinary oncology evaluation context, if an IOERT boost is included as a component of treatment together with preoperative chemoradiation.     

Clinical Outcome for Chemoradiotherapy in Carcinoma of the Cervix

AimsTwo recent meta-analyses have shown a survival advantage for the addition of concurrent chemotherapy to radiotherapy in the treatment of cervical cancer. However, there is insufficient information available on late toxicity and few data from UK practice. The aims of this study were to examine treatment outcomes (survival and toxicity) in patients with cervical cancer treated with chemoradiation and to compare these with outcomes in patients treated with radiation alone.Materials and methodsBetween July 2000 and December 2003, 75 patients with cervical cancer were treated with chemoradiation. Case notes were reviewed retrospectively. Acute and late toxicity were recorded, with late toxicity graded using the Franco-Italian glossary. The median age was 47 years. All patients were staged with examination under anaesthesia and magnetic resonance imaging scans. Forty-two patients were treated with concurrent chemoradiation alone and 33 patients were treated with a combination of neoadjuvant and concurrent chemoradiation. This was due to waiting list problems. The chemotherapy used was cisplatin 40 mg/m² weekly with radiotherapy, (the neoadjuvant dose was 60 mg/m² 3 weekly). External beam radiotherapy was given to the pelvis (40–45 Gy/20 fractions/4 weeks) followed by low dose rate brachytherapy (22.5–32.5 Gy to point A). Patients who were unable to have brachytherapy were given an external beam boost (15–20 Gy/8–10 fractions).ResultsThe 3-year overall survival rate was 70%, with an estimated 5-year overall survival rate of 60%. The 3-year disease-free survival was 63.6%, with an estimated 5-year disease-free survival rate of 55%. Compared with the cohort of 183 patients from the Christie Hospital in a 1993 audit, there was a trend towards improved overall survival from 49 to 60% (P = 0.06), which may become significant with longer follow-up. There were seven patients (9.3%) with grade 3 toxicity and no cases of grade 4 toxicity. In comparison with patients treated in the 1993 audit, the late toxicity rate has increased from 3.4 to 9.3%, but this was not statistically significant (P = 0.14).ConclusionThere was a trend towards improved survival with concurrent chemoradiation in this cohort of patients that may become significant with longer follow-up.     

The Effects of Neoadjuvant Treatment on the Tumor Microenvironment in Rectal Cancer: Implications for Immune Activation and Therapy Response

BackgroundBecause more than one neoadjuvant treatment is available for advanced rectal cancer, the aim of this study was to compare the differential clinical and pathologic effects of different combinations of chemoradiation regimens, treatment sequencing, and timing to surgery on patient outcomes.Patients and MethodsBetween January 2015 and October 2018, 126 newly diagnosed patients with rectal cancer with magnetic resonance imaging-based cT3-4 or N+ rectal disease for curative-intent treatment received 1 of 4 neoadjuvant regimens, followed by immediate surgery or delayed surgery. Whole post-neoadjuvant surgical specimens were assessed by 3-dimensional digital whole-tumor microarray imaging and immunostaining in pathology to analyze the global tumor pathologic regression grades, residual tumor distribution patterns, the extent of lymphovascular permeation, lymph node positivity, and the overall density of lymphocyte infiltration in the tumor microenvironment. These factors were further examined to identify possible correlations with clinical outcomes.ResultsAmong the 4 neoadjuvant treatment groups, including 2 conventional regimens, we found a significant increase of stromal CD3+ and CD8+ immune infiltrates in the postneoadjuvant tumor microenvironment in the 3 groups with delayed surgery after different chemoradiation regimens compared with the group with immediate surgery after a short course of RT alone. Independent of neoadjuvant chemoradiation regimens, the post-induction high-intermediate-low stromal-infiltrating CD8+ T-cell densities corresponded to tumor regression grades, distant metastasis rates, and disease-free survival and were prognostic factors for the further stratification of patients with American Joint Committee on Cancer stage III rectal cancer into different risk groups after surgery.ConclusionThe effectiveness of induction strategies on tumor remission and disease recurrence in advanced rectal cancer was significantly correlated with an enhanced cytotoxic immune response in the tumor microenvironment.