A population based study of radiotherapy in a cohort of patients with breast cancer diagnosed between 1996 and 2000

We studied the use of radiotherapy (RT) (especially secondary RT) in a cohort of 6561 patients in southern Netherlands with invasive breast cancer diagnosed between 1996 and 2000 (median follow-up: 66 months, range 0-107 months). Radiation within 6 months of diagnosis was considered primary RT (PRT). RT given 6 months or later after diagnosis or after PRT was considered secondary RT (SRT). Of all patients, 67% received RT, 3554 only PRT, 323 only SRT and 503 both. The cumulative use of SRT at 100 months was 17%. The 826 patients receiving SRT underwent 1846 courses 0-105 months (median 36) after diagnosis; the retreat rate was 35%. Elderly patients received SRT significantly less often (OR(age50-69)=0.7, 95%CI=0.6-0.8, OR(age> or 70)=0.4, 95%CI=0.3-0.5). The following factors increased the chance for SRT: patients from the eastern region (OR=1.3, 95%CI=1.1-1.6); patients who received PRT (OR=1.3, 95%CI=1.0-1.5) and patients who underwent mastectomy including axillary node dissection as well as unresected patients (OR=1.9, 95%CI=1.5-2.4, OR=2.6, 95%CI=1.7-3.9, respectively). Thirteen percent of all patients with breast cancer received SRT, with a large variation in age and between the 2 RT departments in the region.     

Clinical nature and prognosis of locally recurrent rectal cancer after total mesorectal excision with or without preoperative radiotherapy.

PURPOSE: To document the clinical nature and prognosis of locally recurrent rectal cancer after total mesorectal excision (TME) with or without 5 x 5 Gy preoperative radiotherapy (PRT) and to identify patient-, disease-, and treatment-related factors associated with differences in prognosis after local recurrence. PATIENTS AND METHODS: For 96 Dutch patients with a local recurrence who participated in a multicenter randomized clinical trial, data on treatments and follow-up were gathered from surgeons and radiation and medical oncologists. Twenty-three patients (24%) had previously been treated with PRT plus TME, and 73 patients (76%) had been treated with TME alone. Eighty-one patients (84%) were followed until death; median follow-up time of the alive patients after local recurrence was 21 months (range, 5 to 48 months). RESULTS: Survival after local recurrence in the PRT + TME group was significantly shorter than in the TME group (median survival, 6.1 v 15.9 months; hazard ratio for death, 2.1; P =.008). Patients with a local recurrence in the PRT + TME group had distant metastases more often (74% v 40%; P =.004), underwent surgical resection of local recurrence less often (17% v 35%; P =.11), and received radiotherapy for local recurrence at a total dose >/= 45 Gy less often (4% v 42%; P =.001) than patients without PRT. In a multivariate analysis, the difference in survival after local recurrence between randomization groups was no longer statistically significant (hazard ratio for death of PRT, 1.53; P =.16). CONCLUSION: The clinical nature and prognosis of patients with locally recurrent rectal cancer has changed since the introduction of PRT. The majority of patients who present with a local recurrence after previous PRT have simultaneous distant metastases, and median survival has decreased to 6 months.     

The influence of age and comorbidity on receiving radiotherapy as part of primary treatment for cancer in South Netherlands, 1995 to 2002

BACKGROUND: The objective of this study was to study the influence of age and comorbidity on receiving radiotherapy (RT) in primary treatment of cancer. METHODS: In a population-based setting, the authors calculated the proportion of irradiated patients within 6 months after they received a diagnosis of lung, rectal, breast, or prostate cancer or non-Hodgkin lymphoma (n = 33,369 patients) according to age and comorbidity between 1995 and 2002. Logistic regression analysis was used to adjust for age, comorbidity, gender, and stage. RESULTS: Patients with localized nonsmall cell lung cancer (NSCLC) ages 65 years to > or = 80 years or with comorbid conditions received RT alone significantly more often compared with younger patients (ages 65-79 years: odds ratio [OR], 3.4; age > or = 80: OR, 12.0) and patients without comorbidities (1 comorbid condition: OR, 2.1; > or = 2 comorbid conditions: OR, 2.4). This also applied to patients with nonlocalized NSCLC ages 65 years to 79 years compared with younger patients (OR, 1.4). RT was administered significantly less often to elderly patients with resected rectal cancers (ages 65-79 years: OR, 0.7; age > or = 80 years: OR, 0.4), patients age > or = 80 years with breast cancer after undergoing conserving surgery (OR, 0.1), and patients age > or = 80 years with clinical T1-T3,N0,M0 prostate cancer age (OR, 0.1) compared with younger patients. Patients with breast cancer who underwent breast-conserving surgery received RT significantly less often in the presence of comorbidities (1 comorbid condition: OR, 0.6; > or = 2 comorbid conditions: OR, 0.4). Older patients with aggressive non-Hodgkin lymphoma received only RT as treatment significantly more often compared with younger patients (OR, 3.4). CONCLUSIONS: Comorbidity and age did have influence over whether patients received RT, although, for most tumor types, age appeared to be a stronger predicting factor. Under treatment was observed among patients with breast cancer and rectal cancer.     

Treatment and survival of locally recurrent rectal cancer: A cross-sectional population study 15 years after the Dutch TME trial

IntroductionOptimized treatment of primary rectal cancer might have influenced treatment characteristics and outcome of locally recurrent rectal cancer (LRRC). Subgroup analysis of the Dutch TME trial showed that preoperative radiotherapy (PRT) for the primary tumour was an independent poor prognostic factor after diagnosis of LRRC. This cross-sectional population study aimed to evaluate treatment and overall survival (OS) of LRRC patients, stratified for prior preoperative radiotherapy (PRT) and intention of treatment of LRRC.MethodsAll patients developing LRRC were selected from a collaborative Snapshot study on 2095 surgically treated rectal cancer patients from 71 Dutch hospitals in the year 2011. Cox proportional hazard analysis was performed to determine predictors for OS.ResultsA total of 107 LRRC patients (5.1%) were included, of whom 88 (82%) underwent PRT for their primary tumour. LRRC was treated with initial curative intent in 31 patients (29%), with eventual resection in 20 patients (19%). Median OS was 22 and 8 months after curative and palliative intent treatment, respectively (p < 0.001). Initial CRM positivity and palliative intent treatment were associated with worse OS after LRRC, while prior PRT was not.ConclusionsThis cross-sectional study revealed that rectal cancer patients, who underwent curative resection in the Netherlands in 2011 and subsequently developed local recurrence, were amenable for again curative intent treatment in 29%, with a corresponding median survival of 22 months. Prior PRT was not significantly associated with survival after diagnosis of LRRC.     

Socioeconomic inequalities in the use of radiotherapy for rectal cancer: A nationwide study

Preoperative radiotherapy (PRT) in rectal cancer reduces the risk of local recurrence by at least half but the influence of the socioeconomic status of patients on the use of PRT is little investigated in Europe.

Methods

Individually attained data on civil status, education and income were linked to the Swedish Rectal Cancer Registry 1995-2005 (n = 16,713) and analysed by logistic regression.

Results

Forty-six percentage of the patients received PRT and the crude rate varied with age, gender, civil status, education and income as well as with sublocalisation, stage, type of hospital and health care region. In a multivariate analysis, all civil status groups had PRT to a lesser extent compared with married patients; odds ratio (OR) for unmarried patients was 0.67 (95% confidence interval (CI) 0.59-0.76). Patients with secondary and university education had PRT to the same extent as those with compulsory school (OR 1.04 (0.94-1.15) and 0.92 (0.81-1.06)). The use of PRT was associated with income; OR for patients with income Q1 versus Q4 was 0.76 (0.67-0.86). The inequalities by civil status and income remained unchanged also in groups with a relatively stronger indication for adjuvant radiotherapy, i.e. younger patients and in low rectal cancer.

Conclusion

Unmarried and low-income patients are at increased risk for not receiving PRT in rectal cancer. Comorbidity may explain some differences but increased awareness of the role of non-medical variables for the use of PRT is warranted.     

Clinical study on risk factors related to postoperative recurrence or metastasis of rectal cancer: a retrospective cohort study

BackgroundRectal cancer is usually treated by surgery, but recurrence or metastasis seriously affect the quality of life and survival of patients. Identifying the risk factors for postoperative recurrence or metastasis of rectal cancer has important guiding value for the treatment of rectal cancer. However, the research on risk factors of postoperative recurrence or metastasis of rectal cancer has not been unified.MethodsThe data of all patients undergoing rectal cancer surgery in The Fifth People’s Hospital of Shanghai, Fudan University, from 2016 to 2020 were collected and analyzed. A total of 185 patients were included for statistical analysis and were divided into a recurrence or metastasis group and a non-recurrence or metastasis group. Patients were followed up according to National Comprehensive Cancer Network (NCCN) guidelines by enhanced CT or MRI, and colonoscopy. The cut-off of the research was recurrence, metastasis, or death. Logistic regression analysis and Cox regression analysis were used to analyze the risk factors related to postoperative recurrence or metastasis of rectal cancer, and the survival curve was drawn.ResultsMultiple logistic regression analysis showed involvement of the mesorectal fascia (MRF) [OR (odds ratio) =2.9, 95% confidence interval (CI): 1.16–7.29, P=0.023], nerve and vascular invasion (OR =1.7, 95% CI: 1.08–2.59, P=0.022), intraoperative blood transfusion (OR =3.7, 95% CI: 1.45–9.40, P=0.006), and Dukes staging (OR =2.3, 95% CI: 1.26–4.35, P=0.007) were independent risk factors for postoperative recurrence or metastasis of rectal cancer. Involvement of mesenteric fascia infiltration (OR =11.5, 95% CI: 1.49–88.79, P=0.019) and Dukes stage (OR =3.0, 95% CI: 1.46–6.26, P=0.003) were independent risk factors for liver metastasis, while nerve and vascular invasion (OR =2.4, 95% CI: 1.19–5.00, P=0.015) was an independent risk factor for pulmonary metastasis.ConclusionsPostoperative recurrence or metastasis of rectal cancer is related to many factors. These findings have clinical guiding value and significance for the follow up and prognosis of patients with rectal cancer after surgery. Large-scale prospective clinical studies are needed.     

Does delay in starting treatment affect the outcomes of radiotherapy? A systematic review.

PURPOSE: The objective of this study was to synthesize what is known about the relationship between delay in radiotherapy (RT) and the outcomes of RT. METHODS: A systematic review of the world literature was conducted to identify studies that described the association between delay in RT and the probability of local control, metastasis, and/or survival. Studies were classified by clinical and methodologic criteria and their results were combined using a random-effects model. RESULTS: A total of 46 relevant studies involving 15,782 patients met our minimum methodologic criteria of validity; most (42) were retrospective observational studies. Thirty-nine studies described rates of local recurrence, 21 studies described rates of distant metastasis, and 19 studies described survival. The relationship between delay and the outcomes of RT had been studied in diverse situations, but most frequently in breast cancer (21 studies) and head and neck cancer (12 studies). Combined analysis showed that the 5-year local recurrence rate (LRR) was significantly higher in patients treated with adjuvant RT for breast cancer more than 8 weeks after surgery than in those treated within 8 weeks of surgery (odds ratio [OR] = 1.62, 95% confidence interval [CI], 1.21 to 2.16). Combined analysis also showed that the LRR was significantly higher among patients who received postoperative RT for head and neck cancer more than 6 weeks after surgery than among those treated within 6 weeks of surgery (OR = 2.89; 95% CI, 1.60 to 5.21). There was little evidence about the impact of delay in RT on the risk of metastases or the probability of long-term survival in any situation. CONCLUSION: Delay in the initiation of RT is associated with an increase [corrected] in LRR in breast cancer and head and neck cancer. Delays in starting RT should be as short as reasonably achievable.     

Utilization of radiotherapy for rectal cancer in Greater Western Sydney 1994–2001

Background and purpose: Despite evidence for the efficacy of radiotherapy in stages II and III rectal cancer, utilization rates remain low. The aim of this study is to examine patient, provider and service factors affecting utilization of radiotherapy in rectal cancer patients. Materials and methods: Patients with a diagnosis of curable rectal cancer were identified from the colorectal tumor databases of three Sydney Area Health Services between 1994 and 2001. Data were collected on tumor characteristics such as site and stage, provider factors such as type of surgery and surgeon caseload, and patient factors including socioeconomic status and access to radiotherapy. Results: Thirty‐five percent of stage II and 57% of stage III rectal cancer patients received radiotherapy. Independent determinants of utilization were age less than 70 years (odds ratio, 2.96; 95% confidence interval, 1.75–5.03), high‐volume surgeons (OR, 1.95; 95% CI, 1.17–3.24), stage III disease (OR, 2.06; 95% CI, 1.25–3.41) and abdominoperineal resections (OR, 3.67; 95% CI, 1.94–6.94). Conclusion: Radiotherapy utilization rates remain low. Age, and being referred to a surgeon with a high caseload, has a greater impact on radiotherapy utilization than other provider, socioeconomic or service factors.     

Histological determinants for different types of local recurrence after breast-conserving therapy of invasive breast cancer. Dutch Study Group on local Recurrence after Breast Conservation (BORST)

The purpose of this study was to determine which histological factors are associated with an increased risk for local recurrence in the breast after breast-conserving therapy for early breast cancer (TNM stage I and II) and whether risk patterns vary according to menopausal status and type of local recurrence. Through complete follow-up of the patients of eight regional radiation oncology departments, two cancer institutes and one surgical clinic in The Netherlands, 360 patients were identified with local recurrence in the breast after having received breast-conserving therapy (local tumour excision, axillary dissection and irradiation of the whole breast and a boost to the tumour bed) during the 1980s. For each case, two controls with a follow-up of similar duration without local recurrence were randomly selected. Histological slides of the primary tumour were reviewed. Among premenopausal patients the risk of recurrence for those younger than 35 years was significantly higher than that for premenopausal patients of 45 years or older (relative risk (RR) 2.9; 95% confidence interval (95% CI) 1.3-6.6, P < 0.05). The risk of recurrence at or near the site of the primary tumour was most significantly increased for patients with high grade extensive intraductal component (EIC) adjacent to the primary tumour (RR 4.1; 95% CI 1.7-9.8, P < 0.01). Microscopic margin involvement was an important risk indicator for diffuse recurrence and recurrence in the skin of the breast, especially in the presence of vascular invasion (RR 25; 95% CI 4.0-150, P < 0.001). To prevent local recurrence at or near the site of the primary tumour, local excision with a 1-2 cm margin of healthy tissue and a 15 Gy boost seemed adequate local treatment for patients with well differentiated EIC. In contrast, a wider surgical margin, a higher boost dose or mastectomy should be considered for patients with poorly differentiated EIC. Microscopic margin involvement in the presence of vascular invasion significantly increases the risk of diffuse recurrence or recurrence in the skin.     

Surgical treatment of locally recurrent rectal cancer.

BACKGROUND: The aim of our study was to analyse data of patients treated by salvage surgery for locally recurrent rectal cancer, with emphasis on the question whether salvage surgery is still worthwhile when adjuvant radiotherapy is no longer a treatment option. METHODS: Forty patients (19 males/21 females) treated by surgery with curative intent for locally recurrent rectal carcinoma were analysed. Local recurrence was defined as cancer recurrence within the lower pelvis. Salvage surgery included abdominoperineal resection, abdominosacral resection, exenteration (posterior or total) and local resection. Clinical and pathological factors were analysed to identify prognostic factors for survival. RESULTS: The median overall survival was 25 months (95% CI: 13-37 months) and 5-year survival was 28% (95% CI: 12-45%). The absence of symptoms at the time of recurrence, central localisation and the absence of microscopic involvement of surgical margins, but not additional radiotherapy, were found to be significant independent prognostic factors for better survival after salvage surgery. CONCLUSION: Salvage surgery, alone or in combination with radiotherapy, can achieve radical resection of locally recurrent rectal cancer and can result in long-term survival.     

Incidence of second tumors after treatment with or without radiation for rectal cancer

BackgroundThe aim of this study was to analyze the association between radiation therapy (RT) for rectal cancer and the development of second tumors.Patients and methodsData on all surgically treated non-metastatic primary rectal cancer patients diagnosed between 1989 and 2007 were retrieved from the Netherlands population-based cancer registry. Fine and Gray’s competing risk model was used for estimation of the cumulative incidence of second tumors. Multivariable analysis was conducted using Cox regression.ResultsThe cohort consisted of 29 027 patients of which 15 467 patients had undergone RT. Median follow-up was 7.7 years (range 0–27). Among all 4398 patients who were diagnosed with a second primary tumor, 1030 had one or more pelvic tumors. The standardized incidence risk for any second tumor was 1.16 (95% confidence interval [CI] 1.12–1.19), resulting in 27.7/10 000 excess cancer cases per year in patients treated for rectal cancer compared with the general population. RT reduced the cumulative incidence of second pelvic tumors compared with patients who did not receive RT (subhazard ratio [SHR] 0.77, CI 0.68–0.88). Second prostate tumors were less common in patients who received RT (SHR 0.54, CI 0.46–0.64), gynecological tumors were more frequently observed in patients who received RT (SHR 1.49, CI 1.11–2.00).ConclusionsPatients with previous rectal cancer had a marginally increased risk of a second tumor compared with the general population. Gynecological tumors occurred more often in females who received RT, but this did not result in an overall increased risk for a second cancer. RT even seemed to have a protective effect on the development of other second pelvic tumors, pre-dominantly for prostate cancer. These findings are highly important and can contribute to improved patient counseling.     

Comparative Oncologic Outcomes of Upper Third Rectal Cancers: A Meta-analysis

IntroductionPreoperative radiation combined with mesorectal excision has reduced local recurrence rates in rectal cancer. The role for neoadjuvant therapy in upper third rectal cancer remains unclear. The current study aimed to use meta-analytical techniques to compare outcomes of upper third rectal tumors relative to those of the middle and lower rectum.Materials and MethodsMeta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases were searched for studies comparing outcomes between patients with upper third and more distal rectal cancer undergoing primary resection. Patients receiving neoadjuvant treatment were excluded. Results were reported as odds ratios (ORs) with 95% confidence intervals (95% CIs).ResultsA total of 174 citations were reviewed; 5 studies comprising 3381 patients were included in the analysis. There was no difference in the rate of T3/4 tumors (OR, 1.303; 95% CI, 0.920-1.847; P = .137), lymph node positivity (OR, 1.004; 95% CI, 0.865-1.165; P = .961), and circumferential resection margin positivity (OR, 0.898; 95% CI, 0.556-1.450; P = .660) between upper third and more distal rectal cancers. However local recurrence (OR, 0.495; 95% CI, 0.302-0.811; P = .005) and distant recurrence (OR, 0.613; 95% CI, 0.511-0.734; P < .001) were reduced in patients with upper third rectal cancer.ConclusionsThese data suggest that upper third rectal cancer has reduced local and distant recurrence rates despite similarity in disease stage and margin positivity. Further studies examining effects of neoadjuvant radiation in rectal cancer should consider upper rectal tumors as a distinct entity to middle and lower rectal tumors.     

Radiotherapy of esthesioneuroblastoma

PURPOSE: Only 3% of all malignant intranasal tumors are esthesioneuroblastomas (ENB). As the tumor is very rare, the number of ENB treated in individual departments is small. In order to evaluate the efficacy of radiotherapy (RT), patients' data of 2 centres were analysed with reference to new reports in literature. METHODS AND MATERIALS: From 1981 to 1998, 17 patients with ENB, 8 men and 9 women aged between 6 and 81 years, were treated in the departments of radiotherapy of the universities of Cologne and Muenster. The tumors were Kadish Stage B in 4/17 patients and Stage C in 13/17 patients. Treatment included incomplete surgery and irradiation in 2/17 patients, adjuvant RT postoperatively in 6/17 patients, definitive RT in 7/17 patients and RT after incomplete surgery of recurrent tumors in 2/17 patients. Postoperatively, the median target dose of EBRT was 56 (range 50-60) Gy; for definitive RT it was 58 (range 40-70) Gy. RESULTS: After a median follow-up period of 86 (range 2-208) months 10/17 patients showed no evidence of disease (NED). There were 6 patients treated with radical complete surgery plus postoperative irradiation and 5 of them were NED. There were 7 patients treated with only irradiation and 3 of those patients were NED. Of 2 patients with incomplete surgery and irradiation there was one patient NED. Of 2 patients with incomplete resection of recurrent tumor who received irradiation, there was one patient NED. 2 of the patients with NED died after 22 and 94 months respectively. 4/17 patients died as a result of local recurrence and 2/17 patients as a result of distant metastases (liver, brain). One patient with a recurrent tumor is alive. Median survival of all 17 patients was 94 months. Progressive disease after definitive RT occurred after a median of 11 months. CONCLUSION: Esthesioneuroblastomas are radiocurable tumors. In correlation to literature a primarily complete tumor resection followed by adjuvant RT (50-60 Gy) offers the best disease free survival.     

Occurrence of second cancers in patients treated with radiotherapy for rectal cancer.

PURPOSE: To analyze the occurrence of second cancers in patients with rectal cancer treated with external radiotherapy (RT) in addition to surgery. PATIENTS AND METHODS: The analyses were based on the Uppsala Trial (completed in 1985), with patients randomly assigned to preoperative RT to all stages or postoperative RT for stage II and III cancers, and the Swedish Rectal Cancer Trial (completed in 1990), with patients randomly assigned to preoperative RT or surgery alone. Patients from the trials were matched against the Swedish Cancer Registry. RESULTS: A total of 115 (7%) of the 1,599 patients developed 122 second cancers. More patients treated with RT developed a second cancer (relative risk [RR], 1.85; 95% CI, 1.23 to 2.78). A significant increased risk for second cancers in the RT group was seen in organs within or adjacent to the irradiated volume (RR, 2.04; 95% CI, 1.10 to 3.79) but not outside the irradiated volume (RR, 1.78; 95% CI, 0.97 to 3.27). For the Swedish Rectal Cancer Trial, 20.3% of the RT patients got either a local recurrence or a second cancer, compared with 30.7% of the non-RT patients (RR, 0.55; 95% CI, 0.44 to 0.70). CONCLUSION: An increased risk of second cancers was found in patients treated with RT in addition to surgery for a rectal cancer, which was mainly explained by an increase in the risk of second cancers in organs within or adjacent to the irradiated volume. However, a favorable effect of radiation seemed to dominate, as shown by the reduced risk of the sum of local recurrences and second cancers.     

Feasibility and morbidity of combined hyperthermia and radiochemotherapy in recurrent rectal cancer--preliminary results

BACKGROUND: The local recurrence rate of colorectal cancer has been significantly reduced due to the use of combined radiochemotherapy. Despite this improvement regarding locally advanced tumour recurrences, the treatment strategy for pre-treated patients remains difficult and unresolved. PATIENTS AND METHODS: We analysed treatment and follow-up data of 14 patients with local recurrence of rectal cancer who were treated with radiation therapy (RT), chemotherapy (CT) and regional hyperthermia (RHT) from November 1997 to December 2001. Nine of these patients had received irradiation and CT (= pre-treated patients) in the past. For this group, 30.6-39.6 Gy RT, 5-fluorouracil (5-FU) as a continuous infusion over 5 days per week (350 mg/m(2)/24 h) combined with RHT twice a week was given. The 5 remaining patients (= not pre-treated) received conformal irradiation of 45 Gy with a boost between 9 and 14.4 Gy, combined with continuous infusion of 5-FU on days 1-4, and 29-33 (500 mg/m(2)/ 24 h), and RHT twice a week. Response to therapy was evaluated by means of computed tomography (CT) or magnetic resonance imaging (MRI) and by clinical follow-up. RESULTS: Among 13 evaluated cases, the overall objective response rate was 54% (5 complete responses, 2 partial responses). At mean follow-up of 13.9 months (range 5-32 months) 7 patients were alive. CONCLUSION: The therapeutic regimen appears to be active in the treatment of local recurrences of rectal cancer. Larger-scaled studies are needed to evaluate the potency of hyperthermia in this therapeutic strategy.     

Determinants of axillary recurrence after axillary lymph node dissection for invasive breast cancer.

AIM: This study was undertaken to gain insight into the risk factors for axillary recurrence among patients with invasive breast cancer who underwent breast-conserving treatment or mastectomy and axillary lymph node dissection. METHODS: In a matched case-control design, 59 patients with axillary recurrence and 295 randomly selected control patients without axillary recurrence were compared. Matching factors included age, year of incidence of the primary tumour and postsurgical axillary nodal status. RESULTS: For patients with negative axillary lymph nodes, those with a tumour in the medial part of the breast had a 73% (95% CI: 4-92%) lower risk of axillary recurrence compared to those with a tumour in the lateral part of the breast. For the patients with positive axillary lymph nodes the risk of axillary recurrence was 65% (95% CI: 16-86%) lower for those who had received axillary irradiation compared to those without axillary irradiation. Within the age group <50 years, the risk or axillary recurrence was 82% lower (95% CI: 45-94%) for patients with more than six lymph nodes found in the axillary specimen compared to those with six or less than six lymph nodes. CONCLUSIONS: Although based on a small number of patients, this study indicates that axillary irradiation is effective in reducing the risk of axillary recurrence for patients with positive lymph nodes. This favourable effect only applies to the subgroup with extranodal extension or nodal involvement in the apex of the axilla, as these were the only patients receiving axillary radiation during the study period. Copyright Harcourt Publishers Limited.     

Conservative management of Paget disease of the breast with radiotherapy: 10- and 15-year results

BACKGROUND: At 5-year follow-up, patients with Paget disease of the breast who were treated with breast-conserving surgery (BCS) and radiotherapy (RT) had excellent results. The current report provides 10- and 15-year rates of tumor control in the breast, as well as disease-free and overall survival rates following BCS and RT in a cohort of patients with Paget disease presenting without a palpable mass or mammographic density. METHODS: Through a collaborative review of patients treated with BCS and RT from seven institutions, 38 cases of Paget disease of the breast presenting without a palpable mass or mammographic density were identified. All patients had pathologic confirmation of typical Paget cells at time of diagnosis. Thirty-six of 38 patients had a minimum follow-up greater than 12 months and constitute the study cohort. Ninety-four percent of patients underwent complete or partial excision of the nipple-areola complex and all patients received a median external beam irradiation dose of 50 Gy (range, 45-54 Gy) to the whole breast. Ninety-seven percent of patients also received a boost to the remaining nipple or tumor bed, a median total dose of 61.5 Gy (range, 50.4-70 Gy). RESULTS: With median follow-up of 113 months (range, 18-257 months), 4 of 36 patients (11%) developed a first recurrence of disease in the treated breast only. Two of the four recurrences in the breast were ductal carcinoma in situ (DCIS) only and two were invasive with DCIS. Two additional patients had a recurrence in the breast as a component of first failure. Actuarial local control rates for the breast as the only site of first recurrence were 91% at 5 years (95% confidence interval [CI], 80-100%) and 87% (95% CI, 75-99%) at both 10 and 15 years. Actuarial local control rates for breast recurrence, as a component of first failure, were 91% (95% CI, 80-100%), 83% (95% CI, 69-97%), and 76% (95% CI, 58-94%) at 5, 10, and 15 years, respectively. No clinical factors were identified as significant predictors for breast recurrence. Five-, 10- and 15-year actuarial rates for survival without disease of 97% (95% CI, 90-100%) and 5-, 10-, and 15-year actuarial rates of overall survival of 93% (95% CI, 84-100%) at 5 years and 90% (95% CI, 78-100%) at 10 and 15 years were reported. CONCLUSIONS: These data confirm excellent rates of local control, disease-free survival, and overall survival at 10 and 15 years following BCS and RT for Paget disease of the breast. This study continues to support the recommendation of local excision and definitive breast irradiation as an alternative to mastectomy in the treatment of patients with Paget disease presenting without a palpable mass or mammographic density.     

Are all prostate cancer patients "fit" for salvage radiotherapy?

The indication for salvage radiotherapy (RT) (SRT) in patients with biochemically-recurrent prostate cancer after surgery is based on prostate-specific antigen (PSA) levels at the time of biochemical recurrence. Although there are clear criteria (pT3-pT4 disease and/or positive margins) for the use of adjuvant radiotherapy, no specific clinical or tumour-related criteria have yet been defined for SRT. In retrospective series, 5-year biochemical progression-free survival (PFS) ranges from 35%-85%, depending on the PSA level at the start of RT. Two phase 3 trials have compared SRT with and without androgen deprivation therapy (ADT), finding that combined treatment (SRT+ADT) improves both PFS and overall survival. Similar to adjuvant RT, the indication for ADT is based on tumour-related factors such as PSA levels, tumour stage, and surgical margins. The number of patients referred to radiation oncology departments for SRT continues to rise. In the present article, we define the clinical, therapeutic, and tumour-related factors that we believe should be evaluated before prescribing SRT. In addition, we propose a decision algorithm to determine whether the patient is fit for SRT. This algorithm will help to identify patients in whom radiotherapy is likely to improve survival without significantly worsening quality of life.     

Neo-adjuvant treatment of rectal cancer with capecitabine and oxaliplatin in combination with radiotherapy: a phase II study

BackgroundPreoperative chemoradiation is now standard treatment for stages II–III rectal cancer. Capecitabine (CAP) and oxaliplatin (OX) are synergistic with radiotherapy (RT) and active in colorectal neoplasms.Patients and methodsTwo cycles of CAP 825 mg/m² b.i.d. (days 1–14) and OX 50 mg/m² (days 1 and 8) every 3 weeks were given concomitantly with pelvic conformal RT (45 Gy). Patients with a ≥T3 and/or node-positive rectal tumour were eligible. The pathologic tumour response was defined according to the tumour regression grade (TRG) scale.ResultsForty-six patients were enrolled. Gastrointestinal adverse events were mostly G1–G2; only two patients experienced G3 vomiting and diarrhoea and six patients had G1 peripheral neuropathy. Haematological toxicity was rare. G2 proctitis and anal pain occurred in two patients. Pathological complete response (TRG1) was observed in nine patients (20.9%; 95% CI 8.7%–33.1%); TRG2 in 19 patients (44.2%); TRG3 in 12 patients (27.9%); and TRG4 in three patients (7%). Overall, nine patients recurred: five with distant metastases, one with local recurrence, and three with both local recurrence and distant metastases.ConclusionsCAP–OX–RT as preoperative treatment for rectal cancer induces a remarkable rate of complete or near-complete pathologically documented response and is well tolerated.     

AEG-1 expression is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy: a study in a Swedish clinical trial

Background:

Preoperative radiotherapy (RT) is widely used to downstage rectal tumours, but the rate of recurrence varies significantly. Therefore, new biomarkers are needed for better treatment and prognosis. It has been shown that astrocyte elevated gene-1 (AEG-1) is a key mediator of migration, invasion, and treatment resistance. Our aim was to analyse the AEG-1 expression in relation to RT in rectal cancer patients and to test its radiosensitising properties.

Methods:

The AEG-1 expression was examined by immunohistochemistry in 158 patients from the Swedish clinical trial of RT. Furthermore, we inhibited the AEG-1 expression by siRNA in five colon cancer cell lines and measured the survival after irradiation by colony-forming assay.

Results:

The AEG-1 expression was increased in the primary tumours compared with the normal mucosa independently of the RT (P<0.01). High AEG-1 expression in the primary tumour of the patients treated with RT correlated independently with higher risk of distant recurrence (P=0.009) and worse disease-free survival (P=0.007). Downregulation of AEG-1 revealed a decreased survival after radiation in radioresistant colon cancer cell lines.

Conclusions:

The AEG-1 expression was independently related to distant recurrence and disease-free survival in rectal cancer patients with RT and could therefore be a marker to discriminate patients for distant relapse.