Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial.

BACKGROUND: Since the introduction of breast-conserving treatment, various radiation doses after lumpectomy have been used. In a phase 3 randomised controlled trial, we investigated the effect of a radiation boost of 16 Gy on overall survival, local control, and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost. Here, we present the 20-year follow-up results. METHODS: Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT02295033. FINDINGS: Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17.2 years (IQR 13.0-19.0). 20-year overall survival was 59.7% (99% CI 56.3-63.0) in the boost group versus 61.1% (57.6-64.3) in the no boost group, hazard ratio (HR) 1.05 (99% CI 0.92-1.19, p=0.323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0.65 (99% CI 0.52-0.81, p<0.0001). The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16.4% (99% CI 14.1-18.8) in the no boost group versus 12.0% (9.8-14.4) in the boost group. Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 (79%) of 354 patients in the no boost group versus 178 (75%) of 237 in the boost group. The cumulative incidence of severe fibrosis at 20 years was 1.8% (99% CI 1.1-2.5) in the no boost group versus 5.2% (99% CI 3.9-6.4) in the boost group (p<0.0001). INTERPRETATION: A radiation boost after whole-breast irradiation has no effect on long-term overall survival, but can improve local control, with the largest absolute benefit in young patients, although it increases the risk of moderate to severe fibrosis. The extra radiation dose can be avoided in most patients older than age 60 years. FUNDING: Fonds Cancer, Belgium.

Altered-fractionated radiotherapy in locally advanced head and neck cancer.

PURPOSE OF REVIEW: To revisit the biologic rationale, the clinical methodology, the outcome and perspectives of altered fractionation in head and neck oncology. RECENT FINDINGS: Various prospective trials and meta-analyses clearly underline the major benefit patients with locally advanced disease draw from hyperfractionation and the need for an adequate selection of time-dose factors to optimize therapeutic index for accelerated regimens. In addition, the advent of high-precision techniques such as intensity-modulated radiation therapy is bound to favor the development of more intensive regimens of irradiation in the management of locally advanced head and neck squamous cell carcinomas. SUMMARY: Altered fractionation, both as stand-alone strategy or as part of approaches combining radiation to systemic treatments, is offering a lot of opportunities to the radiation oncologist. Its role is likely to gain ground in all high-risk patients not amenable to systemic treatments, or for whom the high toxicity of chemotherapy is not justified, in case, for instance, of intermediate-risk disease.

[Intraoperative radiation therapy in conservative treatment of breast cancer: Quo Vadis?]. / Radiothérapie intra-opératoire dans le traitement du cancer du sein: Quo Vadis?

Intraoperative radiotherapy of breast carcinomas consists of a single irradiation session delivered to the surgical bed, immediately after the tumor resection. This modality, denoted in the literature as IORT, represents a novel therapeutic approach, the application of which is rigorously codified according to the risk factors identified at the time of diagnosis. As definitive treatment, IORT is applied to patients in post-menopausal status, presenting a small tumor with favorable pathological features. In patients with less favorable presentation (intermediary risk), IORT can be associated to hypofractionated external radiotherapy delivered to the whole mammary gland, on the basis of recommendations proposed by specialty international bodies, in Europe and USA.

Hyperfractionated or accelerated radiotherapy for head and neck cancer.

BACKGROUND: Several trials have studied the role of altered fractionation radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. OBJECTIVES: The aim of this individual patient data (IPD) meta-analysis was to assess whether this type of radiotherapy could improve survival. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; CENTRAL (2010, Issue 3); PubMed; EMBASE; CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN and additional sources for published and unpublished trials. The date of the most recent search was 8 August 2010. SELECTION CRITERIA: We identified randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic head and neck squamous cell carcinomas and grouped trials into three pre-specified treatment categories: hyperfractionated, accelerated and accelerated with total dose reduction. Trials were eligible if they began recruitment after 1969 and ended before 1998. DATA COLLECTION AND ANALYSIS: We obtained updated individual patient data. Overall survival was the main outcome measure. The secondary outcome measures were local or regional control rates (or both), distant control rates and cause-specific mortality. MAIN RESULTS: We included 15 trials with 6515 patients. The median follow up was six years. Tumour sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (UICC 2002). There was a significant survival benefit with altered fractionation radiotherapy, corresponding to an absolute benefit of 3.4% at five years (hazard ratio (HR) 0.92, 95% CI 0.86 to 0.97; P = 0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at five years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at five years, P = 0.02). There was a benefit in locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at five years; P < 0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (under 50 year old) (HR 0.78, 95% CI 0.65 to 0.94), 0.95 (95% CI 0.83 to 1.09) for 51 to 60 year olds, 0.92 (95% CI 0.81 to 1.06) for 61 to 70 year olds, and 1.08 (95% CI 0.89 to 1.30) for those over 70 years old; test for trends P = 0.007). AUTHORS' CONCLUSIONS: Altered fractionation radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation provides the greatest benefit. An update of this IPD meta-analysis (MARCH 2), which will increase the power of this analysis and allow for other comparisons, is currently in progress.

Impact of the boost dose of 10 Gy versus 26 Gy in patients with early stage breast cancer after a microscopically incomplete lumpectomy: 10-year results of the randomised EORTC boost trial.

PURPOSE: To assess the impact of the boost dose in patients with involved surgical margins. PATIENTS AND METHODS: In the EORTC "boost versus no boost" trial, 251 patients with a microscopically incomplete tumour excision were randomised to receive either a low boost dose of 10 Gy (126 patients) or a high boost dose of 26 Gy (125 patients). Overall survival and the cumulative incidence of local recurrence as first event were compared by Logrank and Gray test, respectively (2-sided alpha=0.05), with a median follow-up of 11.3 years. The planned sample size was 660 patients, but only 251 were recruited. RESULTS: The median age at randomisation was 54 years. Thirty-seven patient initially relapsed locally. At 10 years, the cumulative incidence of local recurrence was 17.5% (95% CI: 10.4-24.6%) versus 10.8% (95% CI: 5.2-16.4%) for the low and high boost dose groups, respectively (HR=0.83, 95% CI: 0.43-1.57, Gray p>0.1). Overall, 64 patients have died (25.5%), 47 of them of breast cancer, without a difference in duration of survival between the two groups (HR=0.97, 95% CI=0.59-1.5, p>0.1). Severe fibrosis was palpated in the breast in 1% versus 5% and in the boost area in 3% versus 13% in the low and high boost dose groups, respectively. CONCLUSIONS: There was no statistically significant difference in local control or survival between the high boost dose of 26 Gy and the low boost dose of 10 Gy in patients with microscopically incomplete excision of early breast cancer. Fibrosis, however, was noted significantly more frequently in cases treated with the high boost dose.

Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis.

BACKGROUND: Several trials have studied the role of unconventional fractionated radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. The aim of this meta-analysis was to assess whether this type of radiotherapy could improve survival. METHODS: Randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic HNSCC were identified and updated individual patient data were obtained. Overall survival was the main endpoint. Trials were grouped in three pre-specified categories: hyperfractionated, accelerated, and accelerated with total dose reduction. FINDINGS: 15 trials with 6515 patients were included. The median follow-up was 6 years. Tumours sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (International Union Against Cancer, 1987). There was a significant survival benefit with altered fractionated radiotherapy, corresponding to an absolute benefit of 3.4% at 5 years (hazard ratio 0.92, 95% CI 0.86-0.97; p=0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at 5 years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at 5 years, p=0.02). There was a benefit on locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at 5 years; p<0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (hazard ratio 0.78 [0.65-0.94] for under 50 year olds, 0.95 [0.83-1.09] for 51-60 year olds, 0.92 [0.81-1.06] for 61-70 year olds, and 1.08 [0.89-1.30] for over 70 year olds; test for trends p=0.007). INTERPRETATION: Altered fractionated radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation has the greatest benefit.

Effect of age and radiation dose on local control after breast conserving treatment: EORTC trial 22881-10882.

PURPOSE: To determine whether the effect of an additional "boost" radiation after breast conservative therapy (BCT) on local control depends on age and evaluate the impact of a treatment policy with a threshold for age. PATIENTS AND METHODS: We used data from EORTC 22881-10882 trial, with median follow-up of 77.4 months. Patients receiving BCT and 50Gy whole breast irradiation were randomized to no boost and 16Gy boost (N=5318). RESULTS: In univariate analysis, a boost reduced local failure by a factor of 2 (P<0.0001). Multivariate analysis showed local control increased with age (P=0.0003). There was no evidence that the relative effect of a boost on local control depends on age (P=0.97) However in younger patients the 5-year local failure was higher, therefore the absolute reduction was greater. If the threshold-age for boost treatment were set at 40 years, 8.4% of the study population would receive a boost, resulting in a 5-year local failure of 6.1% in the study population. Changing the threshold-age to 60 years, 67% of the study population would receive a boost and the 5-year local failure would be reduced to 4.4%. CONCLUSIONS: In younger patients a boost dose resulted in a greater absolute reduction of local failure. The relative risk reduction was however similar for all ages. Applying a treatment policy with a threshold-age of 60 would result in 0.6% increase in local failure in the total study population, while sparing the boost to 1/3 of the patients.

Prognostic Factors for Local Control in Breast Cancer After Long-term Follow-up in the EORTC Boost vs No Boost Trial: A Randomized Clinical Trial.

IMPORTANCE: Prognostic factors of ipsilateral breast tumor recurrence (IBTR) may change over time following breast-conserving therapy. OBJECTIVE: The EORTC "boost no boost" trial showed that young age and high-grade invasive carcinoma were the most important risk factors for IBTR. This study reanalyses pathological prognostic factors related to IBTR using long-term follow-up. DESIGN, SETTING, AND PARTICIPANTS: Participants included 5569 early-stage breast cancer patients, treated with breast-conserving surgery (BCS) and whole-breast irradiation (WBI), who were randomized between no boost and a 16-Gy boost in the EORTC phase III "boost no boost" trial (1989-1996). A total of 1616 patients with a microscopically complete resection (according to local pathologists), included in the central pathology review, have been analyzed in this study. Median follow-up was 18.2 years. INTERVENTIONS: No further treatment or 16-Gy boost, after BCS and 50-Gy WBI. MAIN OUTCOMES AND MEASURES: Time to ipsilateral breast tumor recurrence (IBTR) as first event. RESULTS: The 20-year cumulative incidence of IBTR in 1616 patients (160 events observed) was 15% (95% CI, 12%-17%). Young age (P < .001) and presence of ductal carcinoma in situ (DCIS) (HR, 2.15; 95% CI, 1.36-3.38; P = .001) were associated with an increased risk of IBTR in multivariable analysis. The cumulative incidence of IBTR at 20 years was 34% (95% CI, 25%-41%), 14% (95% CI, 10%-18%), and 11% (95% CI, 8%-15%), in patients 40 years or younger, 41 to 50 years and 50 years or older, respectively (P < .001). This incidence was 18% (95% CI, 14%-22%) and 9% (95% CI, 6%-12%) for tumors with and without DCIS (P < .001). High-grade tumors relapsed more frequently early during follow-up but the relative effect of age and presence of DCIS seemed stable over time. The boost reduced the 20-year IBTR incidence from 31% (95% CI, 22%-39%) to 15% (95% CI, 8%-21%) (HR, 0.37; 95% CI, 0.22-0.62; P < .001) in high-risk patients (≤50 years with DCIS present). CONCLUSIONS AND RELEVANCE: The association of high-grade invasive tumor with IBTR diminished during follow-up, while the effect of DCIS adjacent to invasive tumor seemed to remain stable. Therefore, patients with high-grade invasive tumors should be monitored closely, especially in the first 5 years, while additional DCIS is an indication for longer follow-up, emphasizing the importance of long-term trial follow-up to estimate absolute effects accurately. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02295033.

Recent advances in regional treatment of breast carcinoma.

Regional treatment is driven by surgery and radiotherapy in early breast cancer patients as sole or combined modalities. Lymph node dissection, performed in patients with positive sentinel lymph nodes accurately identifies malignant spread in the nodal areas and ensures high levels of control in the axilla. At the turn of the century, its real impact on survival indices was nevertheless questioned, also in terms of therapeutic index, by cooperative groups and meta-analyses. As regards radiotherapy, both the indication and extension of regional irradiation remained for a long time open questions, since these issues were never addressed by randomized trials. Recent results of controlled trials investigating the exact impact of nodal surgery or irradiation on survival indices provide useful tools to optimize the regional treatment in patients with early breast cancer. Caution on interpreting some of the key messages from these controlled studies is nevertheless mandatory due to methodological limitations and caveats identified in several of these major trials enrolling patients with positive sentinel nodes.

Quality assurance in the EORTC phase III randomised 'boost vs. no boost' trial for breast conserving therapy: comparison of the results of two individual case reviews performed early and late during the accrual period.

BACKGROUND AND PURPOSE: To evaluate the impact of quality assurance on treatment compliance, we compared the outcome of the two individual case reviews (ICR) conducted early and late during the accrual period of a large prospective multi-centre trial. PATIENTS AND METHODS: At the onset of the trial, medical files of five patients from each participating centre were evaluated for the compliance to the protocol for eligibility, surgery, pathology and radiotherapy and for the quality of reporting of the data on the case report forms. In nine major centres, this procedure was repeated near the end of the trial. RESULTS: Both in the early and the late ICR, we found a very limited number of deviations from the guidelines for eligibility, staging, surgery, and pathology. Compliance to radiotherapy requirements was good with the exception of a too low minimal dose in 30% and the lack of target volume delineation in the majority of the evaluated patients. The comparison of the late with the early ICR demonstrated an improvement of the quality of data reporting by 6% and of target volume delineation from 33 to 53%. CONCLUSIONS: The initial ICR has lead to the identification of a number of parameters, which needed a clarification in the protocol. These items have been corrected and the individual institutions have been made aware of the necessary adaptations. The evaluation at the end of the trial period showed that there was an improvement but also showed that continuous monitoring is necessary, especially for institutions which have the most deviations in the first ICR.

Prophylaxis versus treatment: is there a better way to manage radiotherapy-induced nausea and vomiting?

Nausea and vomiting are two of the most distressing side effects of radiotherapy and cytotoxic drugs, which currently are often combined to treat moderately advanced and advanced solid tumors. Inadequate control of these symptoms may result in significant patient suffering and decrease in the patient's quality of life, which has been shown to decrease patients' compliance to treatment, with potential impact on disease outcome. It is, therefore, important that radiation oncologists recognize the need for adequate prophylactic treatment of radiation-induced nausea and vomiting (RINV) to avoid the detrimental effects on patients' quality of life, and optimize chances for cure. The 5-hydroxytryptamine type 3 (5-HT(3))-receptor antagonists have been proved to provide effective antiemetic therapy in patients undergoing highly emetogenic radiotherapy. Nevertheless, several large surveys have shown that optimal treatments are not always used. Hence, a risk exists that waiting for RINV symptoms rather than prescribing prophylactic antiemetic treatment may lead to increased patient suffering, poorer disease control, and less cost-effective therapy options. Prophylactic management with an effective 5-HT(3)-receptor antagonist should offer a better treatment option for patients at high to moderate risk of RINV. Adequate control of RINV should contribute to patient compliance to treatment, improved therapy outcomes, and decreased burdens on nursing and health care resources.

Compliance to the prescribed dose and overall treatment time in five randomized clinical trials of altered fractionation in radiotherapy for head-and-neck carcinomas.

PURPOSE: To investigate compliance to the prescribed dose-fractionation schedule in five randomized controlled trials of altered fractionation in radiotherapy for head-and-neck carcinoma. METHODS AND MATERIALS: Individual patient data from 2566 patients participating in the European Organization for Research and Treatment of Cancer (EORTC) 22791, EORTC 22811, EORTC 22851, Princess Margaret Hospital (PMH), and continuous hyperfractionated accelerated radiotherapy (CHART) head-and-neck trials were merged in the fractionation IMPACT (Intergroup Merger of Patient data from Altered or Conventional Treatment schedules) study database. The ideal treatment time was defined as the minimum time required to deliver a prescribed schedule. Compliance to the prescribed overall treatment time was quantified as the difference between the actual and the ideal overall time. An overall measure of compliance in an individual patient, the total dose lost (TDL), was calculated as the dose lost due to prolongation of therapy (assuming a D(prolif) of 0.64 Gy/day) plus the difference between the prescribed and the actual dose given. RESULTS: The time in excess of the ideal ranged up to 97 days (average 3.9 days), and 25% of the patients had delays of 6 days or more. World Health Organization (WHO) performance status and nodal stage had a significant effect on TDL. TDL was significantly higher in the conventional than in the altered arm of the EORTC 22851 and CHART trials. In the PMH trial, TDL was significantly higher in the hyperfractionation than in the conventional arm. Centers participating in the three EORTC trials varied significantly in their compliance. There was a significant improvement in compliance in patients treated more recently. CONCLUSIONS: Even in randomized controlled trials, compliance to the prescribed radiation therapy schedule may be relatively poor, especially after conventional fractionation. This affects the interpretation of the outcome of these trials.

Ultimate results of radiation therapy for T1-T2 mycosis fungoides (including reirradiation).

PURPOSE: We report on our experience in the treatment of T1 and T2 mycosis fungoides (MF) with total skin electron beam therapy (TSEBT), with respect to relapse-free rate, overall survival rate, and management of recurrence. METHODS AND MATERIALS: Between 1975 and 2001, 141 patients with MF were referred to the radiotherapy department for treatment by TSEBT. A total of 57 patients were staged as having T1 or T2 disease (24 T1 and 33 T2 patients). A total of 25 received topical therapy before irradiation. Treatment was delivered through a 6-MeV linear accelerator to a mean total dose of 30 Gy, 2 Gy/day, 4 days/week, for 4 weeks. Close follow-up was initiated without adjuvant therapy. Median age was 61 years (range, 19-84), and median follow-up was 114 months (range, 14-300). RESULTS: Three months after completion of TSEBT, the overall response rate was 94.7%. A complete response was achieved in 87.5% of T1 and 84.8% of T2 patients. Thirty-one patients (54.4%) experienced a skin failure (8 with T1 and 23 with T2 disease) within 1 year. Eighteen patients of 31 received a reirradiation as salvage therapy (6 localized treatment with segmental fields of electron beam irradiation and 12-second TSEB delivering 24 Gy in 12 fractions). Two were treated by topical steroids, and 11 received combination therapy with PUVA (2/10), topical (10/10) or systemic (4/10) chemotherapy, or interferon (7/10). After a second course of TSEBT (4 T1 and 10 T2 patients), the 5-year freedom from relapse rate was 70% vs. 39% in patients having received other modalities. For the whole group, 5-year DFS was 50%. The 5/10/15-year OS were 90%/65%/42%, respectively. In univariate analysis, T1 (p = 0.03), CR after first TSEBT (p = 0.04), and age younger than 60 (p < 0.001) were significant prognostic factor for OS. In multivariate analysis, age younger than 60 years was statistically associated with improved OS (p = 0.001); T stage and completion of CR remained under threshold of significance (p = 0.059 and p = 0.063, respectively). During the mean 86-month period of follow-up from relapse, a second recurrence was observed in 29% of patients. CONCLUSIONS: TSEBT is highly effective in early-stage MF without adjuvant therapy. Management of relapses with local radiotherapy or second TSEBT is feasible, time-saving, and cost-effective.

Treatment of T1-T2 rectal tumors by contact therapy and interstitial brachytherapy.

BACKGROUND AND PURPOSE: We retrospectively analysed our experience of contact therapy alone and/or combined with interstitial brachytherapy as exclusive treatment of low lying rectal tumours. PATIENTS AND METHODS: From 1971 to 2001, 124 patients (103 adenocarcinomas, 21 villous tumours) were treated by contact therapy alone or combined with interstitial brachytherapy. All patients were staged according to the Dijon classification. The average size of the lesions was 2.4 cm (max 7 cm), clinical aspect was polypoïd in 75% of the cases, flat in 17%. Sixty four patients received contact therapy in three fractions and 44 patients received four fractions, for an average delivered dose of 95 Gy. Interstitial brachytherapy boost delivered 24 Gy on a reference isodose of 55 cGy/h in 10 patients. RESULTS: The local control was 83% for T1 and 38% for T2 tumours (p=0.004). For mobile tumours, the local control rate is 76%, significantly higher than for tumours with impaired mobility (55%, P=0.03). Thirty-nine patients experienced a local failure (31%). For patients amenable to surgery, a Miles procedure was performed in 25 patients. Ultimate local control rate is 93% for T1, 69% for T2 (P<0.05), 15 patients failed despite treatment for local recurrence (15%). No significant differences were observed in a comparison of adenocarcinoma and villous tumours according to initial and ultimate local control. The mean disease free survival rate for the whole population is 66 months. The 5-year disease free survival for T1a and T1b is, respectively, 82 and 78%, 40 and 25% for T2a and T2b, respectively. The overall 5-year survival for the whole group is 62.4%. At the end of the treatment, 75% of the patients described a very good sphincter function. No deleterious effect on continence was reported during the follow-up. CONCLUSIONS: The control rate for T1 rectal cancer treated with contact therapy with or without brachytherapy is comparable to surgical series. The sphincter was preserved in 80% of the patients. Radiotherapy remains an efficient and cheap alternative to surgery, mainly for old and fragile patients, or refusing colostomy. The results of these approaches for tumors larger than 3 cm (T2) are not satisfactory. For patients not amenable to surgery, external beam radiation therapy and/or combined modality with chemoradiation should be discussed to increase the loco-regional control rate. A careful selection of patients based on rectal examination and trans-rectal ultrasound could select more accurately patients amenable to such an approach.

The influence of the boost technique on local control in breast conserving treatment in the EORTC 'boost versus no boost' randomised trial.

BACKGROUND AND PURPOSE: The EORTC Trial 22881/10882 investigating the role of a boost dose in breast conserving therapy demonstrated a significantly better local control rate with the higher radiotherapy dose, especially in women younger than 50 years of age. This paper investigates the potential impact of the different boost techniques on local control and on fibrosis after breast conserving therapy. PATIENTS AND METHODS: From 1989 to 1996, 2661 patients were randomised to receive a boost dose of 16Gy to the primary tumour bed after microscopically complete tumorectomy and 50Gy whole breast irradiation. The choice of the boost technique was left to the treating investigator. Treatment data were prospectively recorded as well as the clinical outcome in terms of local control and fibrosis. Sixty-three percent of the patients received a boost dose with fast electrons, 28% with photon beams and 9% with interstitial brachytherapy. RESULTS: At 5 years, local recurrences were seen in 74 of the 1635 patients who received an electron boost (4.8%, CI 3.6-5.9%), in 28 of the 753 patients who received a photon boost (4.0%, CI 3.4-5.5%) and in 6 of the 225 patients after an interstitial boost (2.5%, CI 0.3-4.6%). The grade of fibrosis in the whole breast as well as at the primary tumour bed, as scored by the treating radiation oncologist, was similar in the three groups. CONCLUSIONS: Although the three groups are of a rather unequal size, the results of the interstitial boost seem similar in terms of fibrosis and at least as good in terms of local control, despite a lower treatment volume and a longer overall treatment time.

Endometrial carcinomas: which radiotherapy for which patient?

Endometrial cancer is the third most common malignancy in women. The endometrioid adenocarcinomas represent 75% to 80% of the pathological subtypes. Ninety per cent of the lesions are stages I or II at diagnosis. Treatment strategies are based on surgery and radiotherapy, but the respective place of external irradiation and intracavitary brachytherapy is not strictly established. The role of pelvic lymphadenectomy and the role of chemotherapy for aggressive histologies or locally advanced disease remain also controversial issues. The question <> is still debatable. Hence, although the answers we will provide may clarify some issues, they will not remove all uncertainties.

Larynx preservation: what is the standard treatment?

Locally advanced laryngeal and hypo-pharyngeal cancers have a rather poor prognosis. Up until the early 1990s, standard treatment was total laryngectomy, with dramatic functional and social outcome. The introduction of cisplatin based chemotherapy made concurrent chemo-radiotherapy (CCRT) the standard treatment for selected patients, fit for an organ preservation strategy. Over two decades of improvement in nonsurgical management of locally advanced laryngeal cancer is reviewed, including the most recent improvements with the introduction of taxanes and anti-EGFR targeted therapy.