Hypofractionated radiotherapy for breast cancer patients treated by breast-conserving surgery: short-term morbidity and preliminary results

Background  

Hypofractionated adjuvant radiotherapy (RT) in breast cancer patients treated by conservative surgery has been increasingly used in recent years. We present our experience regarding tolerance/acute toxicity of a hypofractionated RT schedule.     

Role of radiation therapy in the conservative management of sarcoma within an irradiated field

Purpose

To report on clinical outcome and toxicity profile after combined treatment that included radiation therapy (RT) in patients with localized sarcoma within an irradiated field.

Patients and methods

Individual clinical data from all consecutive patients diagnosed and treated for a localized SIF between January 2000 and October 2011 at the Institut Claudius Regaud, Toulouse, France, were retrospectively reviewed. Outcomes of patients with SIF who underwent adjuvant or definitive radiotherapy were compared with patients who did not receive further RT.

Results

Of the 27 patients eligible for this study: surgery alone (S), surgery followed by RT (S + RT) or definitive RT (RT) was performed in 16, 8 and 2 cases respectively. The rate of unresectable, gross or microscopically positive margin disease among the 10 re-irradiated patients was significantly higher than the non re-irradiated group (90% vs. 12% p < 0.001). After a median follow-up of 3.8 years, there was a trend toward longer survival and better local control in the subgroup of patients who received adjuvant or definitive RT compared to the rest of the cohort with an acceptable toxicity profile. The 4-year relapse free survival rates of patients treated with and without RT were 53% and 27% respectively (p = 0.09).

Conclusion

SIF complete surgical resection is often difficult to achieve, enhancing the risk of relapse. RT should be discussed in case of unresectable tumor or after suboptimal surgery as part of intensified local management that has a curative intent.     

Letrozole sensitizes breast cancer cells to ionizing radiation

Introduction  

Radiotherapy (RT) is considered a standard treatment option after surgery for breast cancer. Letrozole, an aromatase inhibitor, is being evaluated in the adjuvant setting. We determined the effects of the combination of RT and letrozole in the aromatase-expressing breast tumour cell line MCF-7CA, stably transfected with the CYP19 gene.     

Repeat lumpectomy for ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery: the impact of radiotherapy on second IBTR

Objectives

There are limited data on the outcomes of patients treated with repeat lumpectomy at the time of ipsilateral breast tumor recurrence (IBTR). Especially, the impact of radiotherapy (RT) on a second IBTR is unknown.

Methods

We retrospectively analyzed 143 patients from 8 institutions in Japan who underwent repeat lumpectomy after IBTR. The risk factors of a second IBTR were assessed.

Results

The median follow-up period was 4.8 years. The 5-year second IBTR-free survival rate was 80.7 %. There was a significant difference in the second IBTR-free survival rate according to RT (p = 0.0003, log-rank test). The 5-year second IBTR-free survival rates for patients who received RT after initial surgery, RT after salvage surgery, and no RT were 78.0, 93.5, and 52.7 %, respectively. Multivariate analysis revealed that RT was a significantly independent predictive factor of second IBTR-free survival.

Conclusion

Repeat lumpectomy plus RT is a reasonable option in patients who did not undergo RT at the initial surgery. In contrast, caution is needed when RT is omitted in patients who have undergone repeat lumpectomy.     

Radiation therapy versus surgery for patients with cervical squamous cell carcinoma who have undergone neoadjuvant chemotherapy revisited

Background

The therapeutic significance of neoadjuvant chemotherapy (NAC) followed by radiation therapy (RT) was negated during the early 1990s. Here, we compared post-NAC RT to surgery for chemo-sensitive cervical squamous cell carcinoma (SCC).

Methods

This study included 79 consecutive patients with cervical SCC who were treated by NAC followed by surgery (n = 49) or by definitive RT (n = 30). We compared characteristics and survival outcomes between the surgery and RT groups by their responses to NAC.

Results

Of the 79 patients, 70 (89%) had stage II–IV disease and 41 (52%) had radiological pelvic lymph node enlargement. The 5-year disease-specific survival (DSS) rate of the entire cohort was 66.4% (median follow-up 54 months). Fifty-five patients (70%) achieved sufficient (complete or partial) responses to NAC. Among patients with insufficient NAC responses, the 5-year DSS rate of the surgery group (55.6%) was significantly higher than the RT group (20.0%; P = 0.044). However, among patients with sufficient responses to NAC, 5-year DSS rates did not significantly differ between the surgery and RT groups (82.3 vs 78.6%; P = 0.79) even though the RT group had many more unfavorable prognostic factors and received fewer subsequent treatments than the surgery group.

Conclusions

Post-NAC survival outcomes among patients with chemo-sensitive cervical SCC who then underwent RT were not inferior to those treated with surgery, and NAC did not detract from the efficacy of subsequent RT. Among selected patients who respond favorably to NAC, RT could be a less invasive substitute for surgery without compromising treatment outcomes.

     

Outcomes of malignant tumors of the lacrimal apparatus: the University of Texas MD Anderson Cancer Center experience

BACKGROUND:

Malignant epithelial neoplasms of the lacrimal apparatus are rare and are typically treated with surgery and occasionally adjuvant radiation therapy (RT). The purpose of this study was to assess treatment outcomes by type of surgery (orbital exenteration vs eye‐sparing surgery) and clarify the role of adjuvant RT for this rare disease.

METHODS:

Forty‐six patients with malignant epithelial neoplasms of the lacrimal apparatus were treated at a single institution from 1945 through 2008. Twenty‐seven patients (59%) were treated with orbital exenteration and 19 (41%) with eye‐sparing surgery; 64% of the orbital exenteration group and 83% of the eye‐sparing surgery group also received adjuvant RT (median dose, 60 grays). Median follow‐up time for all patients was 38 months (range, 3‐460 months).

RESULTS:

For the orbital exenteration and eye‐sparing surgery groups, the 5‐year overall survival (OS) rates were 59% and 62%, and the 5‐year disease‐free survival (DFS) rates were 49% and 39%, respectively (P = .56, P = .35). Tumor status (T1‐2 vs T3‐4) was associated with OS (P = .02), and tumor size (<3.5 vs >3.5 cm) with DFS (P = .015). Median time to locoregional recurrence was 85 months for orbital exenteration, and 123 months for eye‐sparing surgery. All patients who did not receive RT experienced local recurrence, and RT extended time to locoregional recurrence (median 460 vs 30 months, P = .009). Seven grade ≥3 complications were experienced after adjuvant RT.

CONCLUSIONS:

For appropriately selected patients, an eye‐sparing surgery for lacrimal apparatus tumors can achieve similar survival outcomes to those in patients treated with an orbital exenteration. Adjuvant RT should be considered for all patients presenting with these rare tumors. Cancer 2011. © 2011 American Cancer Society.     

Salvage radiotherapy for patients with PSA relapse after radical prostatectomy: a single institution experience

Background  

To assess the efficacy of salvage radiotherapy (RT) for persistent or rising PSA after radical prostatectomy and to determine prognostic factors identifying patients who may benefit from salvage RT.     

Impact of timing of radiation therapy on outcomes in atypical meningioma: A clinical audit

Background

The role of early adjuvant radiation therapy (RT) in patients with atypical meningioma remains controversial. The goal of this work was to report the impact of timing of RT on outcomes in atypical meningioma.

Do radiation use disparities influence survival in patients with advanced breast cancer?

BACKGROUND:

The authors previously identified racial/ethnic disparities in the use of radiation therapy (RT) in patients with advanced breast cancer (BC). They hypothesized that disparities in the use of RT were associated with survival differences favoring white patients.

METHODS:

The authors used the Surveillance, Epidemiology, and End Results database to identify white, black, Hispanic, and Asian patients with BC associated with ≥10 metastatic lymph nodes diagnosed between 1988 and 2005. Multivariate analyses of overall survival (OS) and disease‐specific survival (DSS) assessed age, sex, race, tumor size, histology, estrogen receptor status, progesterone receptor status, RT, and type of surgery. The authors further stratified for use of RT and type of surgery. Risk of mortality was reported as hazard ratios (HRs) with 95% confidence intervals (CIs).

RESULTS:

Of 15,895 patients with advanced BC, 12,653 met entry criteria. On multivariate analysis, RT was associated with a decreased risk of all‐cause (HR, 0.78; 95% CI 0.74‐0.83; P < .001) and disease‐specific (HR, 0.81; 95% CI, 0.76‐0.86; P < .001) mortality; black race was associated with an increased risk of all‐cause (HR, 1.54; 95% CI, 1.42‐1.68; P < .001) and disease‐specific (HR, 1.53; 95% CI, 1.39‐1.68; P < .001) mortality. After stratifying by type of surgery and use of RT, blacks demonstrated poorer survival than their white counterparts, regardless of surgery type or receipt of RT.

CONCLUSIONS:

Only black patients had poorer OS and DSS relative to whites. When stratified by type of surgery and use of RT, blacks continued to demonstrate poorer survival. This survival disparity is unlikely to be because of lack of RT. Cancer 2012;. © 2011 American Cancer Society.     

A prospective observational cohort study examining the development of head and neck lymphedema from the time of diagnosis

Introduction

Head and neck lymphedema can occur in the internal or external structures of the head and neck region. Little is known about the development of this condition over the course of treatment for head and neck cancer. This study aimed to observe the development of internal and external lymphedema from diagnosis to 12 weeks postacute treatment.

Methods

A single center, prospective observational cohort study assessed participants for external lymphedema, internal lymphedema, quality of life, and symptom burden. Assessments were conducted prior to starting radiotherapy (RT), at the end of RT, 6 and 12 weeks after RT.

Results

Forty-six participants were recruited. External lymphedema as measured by percentage water content, increased from 41.9 at baseline (95% CI: 39.3–44.4) to 50.4 (95% CI: 46.0–54.8) at 12 weeks following RT (p-value < .001). After adjusting for changes in weight and participant age at baseline, a general increase in tape measurements was observed over time with significant increases from baseline to 12 weeks post-RT for all measurement points. By 12 weeks post-RT, all participants had lymphedema present in eight of 13 internal sites assessed.

Conclusions

Internal and external head and neck lymphedema was observed to increase from baseline to 12 weeks after completion of RT without abatement. People with head and neck cancer should be educated about the potentially extended duration of this treatment side effect. Further research is required to determine the point at which swelling symptoms recede.     

Neoadjuvant treatment improves capsular integrity and the width of the fibrous capsule of high-grade soft-tissue sarcomas

Background

Neoadjuvant treatment is thought to improve resection with margin-negative surgery in locally advanced soft-tissue sarcomas (STS). Treatment-induced alterations of the tumor peripheryhave not yet been microscopically evaluated.

Objective

This histopathological study compared limb STS with primary resection and those that had undergone neoadjuvant treatment, emphasizing microscopic changes of the fibrous capsule (FC) and reactive zone (RZ) after neoadjuvant treatment.

Patients and methods

Patients with primary high-grade limb sarcomas (N = 76) which have not previously been treated were included. Of those, 37 were primarily resected and 39 were treated with one of the following neoadjuvant treatment modalities: 7x chemotherapy (CTX), 3x radiotherapy (RT), 15x isolated limb perfusion (ILP), 8x CTX + RT, and 6x CTX + ILP. Sizes of the FC and RZ were microscopically measured, and FC-integrity was documented. Histopathologic regression was expressed as a percent.

Results

Only 35.1% of untreated sarcomas showed an intact FC. We observed significantly higher capsular integrity after treatment (76.9%). Additionally, the average width of the FC (0.21 mm vs. 0.61 mm) and RZ (0.67 mm vs. 1.48 mm) increased significantly. The extent of histopathologic regression showed a correlation with capsular integrity and width. The combination of two treatment modalities (CTX + RT or ILP) showed strongest effects at the tumor periphery.

Conclusions

Neoadjuvant treatment stabilizes the tumor periphery in STS (e.g., the capsule). Concerning local treatment strategies, these novel histopathologic insights might significantly influence the decision as to whether primary resection is advisable in advanced local soft-tissue sarcoma.     

The position and current status of radiation therapy after primary systemic therapy in breast cancer: a national survey-based expert consensus statement

Background

Primary systemic therapy (PST) is changing the role of radiation therapy (RT) in breast cancer. Without randomized studies, the optimal indications for RT after PST and surgery are not clear. The present study provides consensus-based recommendations to clarify the role of RT.

Methods

Radiation oncologists (n = 82; 77 % response rate) in Spain were surveyed to determine their recommendations for locoregional RT following PST and surgery.

Results

Most (98 %) specialists support whole breast irradiation after breast-conserving surgery (BCS), regardless of pathologic response to PST. In T1–T2 and T3–T4 tumours with sentinel node biopsy (SNB) prior to PST, 91 and 56 % of respondents, respectively, recommend irradiating the supraclavicular (level IV) and axillary level III nodes when nodal involvement is detected (9 and 44 % of respondents recommend irradiating these areas by independent of nodal status). If SNB is not available, 57 and 30 % of specialists agreed that the aforementioned nodal regions should be irradiated (33 and 65 % of respondents recommend irradiating these areas by independent of nodal status). Between 58 and 76 % of specialists agreed that nodal levels I and II should be irradiated in cases of insufficient lymphadenectomy or when >75 % of the resected nodes are involved.

Conclusion

Agreement is strong regarding the indications for local RT after PST and surgery, but less so for nodal irradiation. All patients who undergo BCS should receive RT, even with complete pathologic response. After mastectomy, RT is recommended in all node-positive stage III cases. Prospective studies will clarify indications for RT in this patient population.

     

Clinical practice and outcome of radiotherapy for esophageal cancer between 1999 and 2003: the Japanese Radiation Oncology Study Group (JROSG) Survey

Background  

To determine the clinical results of radiotherapy (RT) for esophageal cancer in Japan.     

Prospective Phase I Study of Capecitabine and Oxaliplatin Concurrent with Radiation Therapy for the Treatment of Locally Advanced Pancreatic Adenocarcinoma,and Retrospective Comparison to Concurrent 5-Fluorouracil/Radiation and Gemcitabine/Radiation

Purpose  

The aims of this study is to determine the maximum tolerated dose of capecitabine and oxaliplatin (CAPOX) delivered concurrent with radiation therapy (RT) in the treatment of locally advanced pancreatic adenocarcinoma and to retrospectively compare outcomes with this regimen to concurrent 5-fluorouracil or capecitabine with RT (5FU-RT) or concurrent gemcitabine-based chemotherapy with RT (GEM-RT).     

Omission of radiation therapy after breast-conserving surgery in the United States: a population-based analysis of clinicopathologic factors

BACKGROUND:

Radiation therapy (RT) after breast‐conserving surgery (BCS) is associated with a significant reduction in ipsilateral breast tumor recurrence and breast cancer mortality rates in patients with early stage breast cancer. The authors of this report sought to determine which patients with breast cancer do not receive RT after BCS in the United States.

METHODS:

The Surveillance, Epidemiology, and End Results registry was used to determine the rates of RT after BCS for women with stage I through III breast cancer in the United States from 1992 through 2007. A multivariate analysis was performed to identify independent predictors of omission of RT.

RESULTS:

In total, 294,254 patients with invasive, nonmetastatic breast cancer were identified who underwent surgery from 1992 through 2007. Most patients (57%) underwent BCS; among those, 21.1% did not receive RT after BCS. The omission of RT increased significantly from 1992 (15.5%) to 2007 (25%). The receipt of RT also decreased significantly for patients with increased cancer stage, age <55 years, high‐grade tumors, large tumors, positive or untested lymph node status, African American or Hispanic race, and negative or unknown estrogen receptor status. Significant geographic variation was observed in the rates of RT after BCS.

CONCLUSIONS:

The omission of RT after BCS was more common in recent years, especially among women who had an increased risk of breast cancer recurrence. This trend represents a serious health care concern because of the potential increased risk of local recurrence and breast cancer mortality. Cancer 2012. © 2011 American Cancer Society.     

Comparison of treatment results between surgery alone, preoperative short-course radiotherapy, or long-course concurrent chemoradiotherapy in locally advanced rectal cancer

Background

The aim of this study is to compare the results between surgery alone, preoperative radiotherapy (RT), or preoperative concurrent chemoradiotherapy (CCRT) followed by surgery in the treatment of locally advanced rectal cancer in Asian patients.

Methods

This study included 151 consecutive patients with clinical T3, T4 or node-positive rectal cancer from Jan. 2005 to Dec. 2007. Eighty-six patients underwent total mesorectal excision (TME) alone, 28 patients received preoperative RT (25?Gy in 5 fractions) followed by TME in 1?week, and 37 patients received preoperative CCRT (50.4?Gy in 28 fractions) followed by TME in 4–6?weeks.

Results

The 3-year loco-regional recurrence (LRR), distant metastasis, overall and disease-free survival rates are comparable among Surgery, RT and CCRT groups. By multivariate analysis, pT4, distal margin <2?cm, the ratio of positive lymph nodes to totally dissected lymph nodes ≥0.2, and non-R0 resection were significant factors for LRR. In subgroup analysis, TME alone produced comparable LRR to RT or CCRT (3.3 vs.. 4.8%) for favorable patients (0–1 risk factors). For unfavorable patients (2 or more risk factors), the LRR rose to 37% in patients receiving surgery alone as compared with 15% in the RT or CCRT patients.

Conclusions

Preoperative RT or CCRT followed by TME produced good local control in favorable and unfavorable patients with locally advanced rectal cancer. If preoperative RT or CCRT is not given, TME alone has a high incidence of local recurrence in unfavorable patients with 2 or more risk factors.     

Long-term outcome of patients with spinal myxopapillary ependymoma: treatment results from the MD Anderson Cancer Center and institutions from the Rare Cancer Network

Background

Spinal myxopapillary ependymomas (MPEs) are slowly growing ependymal gliomas with preferential manifestation in young adults. The aim of this study was to assess the outcome of patients with MPE treated with surgery, radiotherapy (RT), and/or chemotherapy.

Methods

The medical records of 183 MPE patients (male: 59%) treated at the MD Anderson Cancer Center and 11 institutions from the Rare Cancer Network were retrospectively reviewed. Mean patient'' age at diagnosis was 35.5 ± 15.8 years. Ninety-seven (53.0%) patients underwent surgery without RT, and 86 (47.0%) were treated with surgery and/or RT. Median RT dose was 50.4 Gy. Median follow-up was 83.9 months.

Results

Fifteen (8.2%) patients died, 7 of unrelated cause. The estimated 10-year overall survival was 92.4% (95% CI: 87.7–97.1). Treatment failure was observed in 58 (31.7%) patients. Local failure, distant spinal relapse, and brain failure were observed in 49 (26.8%), 17 (9.3%), and 11 (6.0%) patients, respectively. The estimated 10-year progression-free survival was 61.2% (95% CI: 52.8–69.6). Age (<36 vs ≥36 y), treatment modality (surgery alone vs surgery and RT), and extent of surgery were prognostic factors for local control and progression-free survival on univariate and multivariate analysis.

Conclusions

In this series, treatment failure of MPE occurred in approximately one third of patients. The observed recurrence pattern of primary spinal MPE was mainly local, but a substantial number of patients failed nonlocally. Younger patients and those not treated initially with adjuvant RT or not undergoing gross total resection were significantly more likely to present with tumor recurrence/progression.     

Multimodality therapy for locoregional extrahepatic cholangiocarcinoma

BACKGROUND:

Although surgical resection is the mainstay of treatment for extrahepatic cholangiocarcinoma, the majority of patients present with advanced disease. Due in part to numeric rarity, the optimum role of radiotherapy (RT) for extrahepatic cholangiocarcinoma, as well as its relative benefit, is an area of debate. The specific aim of this series was to estimate survival for extrahepatic cholangiocarcinoma patients receiving surgery and adjuvant RT using a robust population‐based data set.

METHODS:

Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) limited‐use data set for selected extrahepatic cholangiocarcinoma cases. Lognormal multivariate survival analysis was implemented to estimate survival for patients for treatment cohorts based on extent of surgical intervention and RT.

RESULTS:

Parametric estimated median survival for patients receiving total/radical resection + RT was 26 months; it was 25 months for total/radical resection alone, 25 months for subtotal/debulking resection + RT, 21 months for subtotal/debulking resection, 12 months for RT alone, and 9 months for those not receiving surgery or RT. Parametric multivariate analysis revealed age, American Joint Committee on Cancer Stage, grade, and surgical/radiation regimen as statistically significant covariates with survival. Surgery alone and adjuvant RT cohorts demonstrated evidence of improved survival compared with no treatment; comparatively, RT alone was associated with survival decrement. Early improvement in survival in adjuvant cohorts was not observed at later time points.

CONCLUSIONS:

Survival estimates using SEER data suggest an early survival advantage for adjuvant RT for patients with locoregional extrahepatic cholangiocarcinoma. Although future prospective series are needed to confirm these observations, SEER data represent the largest domestic population‐based extrahepatic cholangiocarcinoma cohort, and may provide useful baseline survival estimates for future studies. Cancer 2009. Published 2009 by the American Cancer Society.     

Impact of radiotherapy delay on survival in glioblastoma

Background

Previous studies in glioblastoma have concluded that there is no decrease in survival with increasing time to initiation of RT up to 6 weeks after surgery. Unfortunately, the number of glioblastoma patients who start RT beyond 6 weeks is not small in some countries. The aim of our study was to evaluate the effect of RT delay beyond 6 weeks on survival of patients who have undergone completed resection of a glioblastoma.

Methods

We reviewed 107 consecutive glioblastoma patients who had a complete surgical resection at our hospital. Clinical data, including delay in initiation of RT, were prospectively collected. The impact of single parameters on overall survival was determined by univariate and multivariate analyses.

Results

According to univariate analysis, variables that had a prognostic influence on survival were age (p = 0.036), KPS (p = 0.031), additional treatment with CHT (p < 0.0001), and initiation of RT before 42 days (p = 0.009). Multivariate analysis indicated that Karnofsky performance scale, additional treatment with chemotherapy, and initiation of RT before 6 weeks after surgery were favorable, independent prognostic factors of survival.

Conclusions

Survival is significantly reduced in glioblastoma patients if RT is not initiated within the 6 weeks after complete resection of the tumor.     

Radiotherapy quality assurance review for a multi-center randomized trial of locally advanced esophageal cancer: the Japan Clinical Oncology Group (JCOG) trial 0303

Background and purpose  

The purpose of this study was to evaluate the radiotherapy (RT) quality assurance (QA) for JCOG 0303.