Prognostic factors of ipsilateral breast tumor recurrence (IBTR) may change over time following breast-conserving therapy.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.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.No further treatment or 16-Gy boost, after BCS and 50-Gy WBI.Time to ipsilateral breast tumor recurrence (IBTR) as first event.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).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.clinicaltrials.gov Identifier: NCT02295033.
Recent treatment patterns for small cell lung cancer (SCLC) in the Netherlands were unknown. This nationwide population-based study describes trends and variations in the treatment of stage I-III SCLC in the Netherlands over the period 2008-2019.Patients were selected from the population-based Netherlands Cancer Registry. Treatments were studied stratified for clinical stage. In stage II-III, factors associated with the use of concurrent (cCRT) versus sequential chemoradiation (sCRT) and accelerated versus conventionally fractionated radiotherapy in the context of cCRT were identified.In stage I (N = 535), 29% of the patients underwent surgery in 2008-2009 which increased to 44% in 2018-2019. Combined use of chemotherapy and radiotherapy decreased in stage I from 47% to 15%, remained constant (64%) in stage II (N = 472), and increased from 57% (2008) to 70% (2019) in stage III (N = 5,571). Use of cCRT versus sCRT in stage II-III increased over time (odds ratio (OR) 2008-2011 vs 2016-2019: 0.53 (95%-confidence interval (95%CI): 0.41-0.69)) and was strongly associated with lower age, WHO performance status 0, and diagnosis in a hospital with in-house radiotherapy. Forty-six percent of patients with stage III received cCRT in 2019. Until 2012, concurrent radiotherapy was mainly conventionally fractionated, thereafter a hyperfractionated accelerated scheme was administered more frequently (57%). Accelerated radiotherapy was strongly associated with geographic region (ORsouth vs north: 4.13 (95%CI: 3.00-5.70)), WHO performance (OR1 vs 0: 0.50 (95%CI: 0.35-0.71)), and radiotherapy facilities treating ≥ 16 vs < 16 SCLC patients annually (OR: 3.01 (95%CI: 2.38-3.79)).The use of surgery increased in stage I. In stages II and III, the use of cCRT versus sCRT increased over time, and since 2012 most radiotherapy in cCRT was accelerated. Treatment regimens and radiotherapy fractionation schemes varied between patient groups, regions and hospitals. Possible unwarranted treatment variation should be countered.
The PORT investigators1PORT Meta-analysis Trialists GroupPostoperative radiotherapy in non-small cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials.Lancet. 1998; 352: 257-263Summary Full Text Full Text PDF PubMed Scopus (833) Google Scholar conclude that postoperative radiotherapy should not be routinely used to treat patients with completely resected early stage NSCLC. Alastair Munro2Munro AJ What now for postoperative radiotherapy for lung cancer?.Lancet. 1998; 352: 250-251Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar advises treatment of patients with a linear accelerator with a dose not greater than 45 Gy in 20 fractions (biological equivalent dose [BED] 79 Gy) or its biological equivalent. In addition, he states that another generation of trials is needed to address the issue of whether postoperative radiotherapy is beneficial or not. The role of postoperative radiotherapy in the treatment of patients with completely resected NSCLC is not yet established. However, a comparison with successful postoperative radiotherapy of, for example, mammary carcinoma forced itself to continue. We doubt whether a meta-analysis such as PORT can provide an answer to this relevant matter. We have several points to make.First, we think that it is not appropriate to refer to unpublished data. The reasons why these studies were not published in unknown. Second, it is inappropriate that patients excluded in the original published analyses were reinstated in the meta-analysis without justification of the reason for doing so. Third, no information is presented for the extent of mediastinal nodal resection. Improvement in survival has been shown when extensive surgical excision of mediastinal nodes is undertaken.3Emami B Management of hilar and mediastinal lymph nodes with radiation therapy in the treatment of lung cancer.in: Meyer J Frontiers in radiation therapy and oncology, vol 28. S Karger, Basel1994Google ScholarFourth, treatment with cobalt is now judged obsolete, especially because of variations in dose. In only two studies was a linac used exclusively. In only two studies was a lung-factor correction applied (EORTC 08861; Lille). However, in the Lille trial dose was prescribed at the 90% isodose. Therefore actual lung doses were larger4Orton CG Chungbin S Klein EE Gillin MT Schultheiss TW Sause WT Study of lung density corrections in a clinical trial (RTOG 88–08).Int J Radiat Oncol Biol Phys. 1998; 41: 787-794Summary Full Text Full Text PDF PubMed Scopus (38) Google Scholar in 95% of all cases than noted in this analysis. Nor do the PORT investigators mention how patients who were assigned to postoperative radiotherapy but who did not actually receive radiotherapy were handled in the analysis. In our opinion, these patients should be excluded from further analysis.Fifth, causes of death other than cancer are not specified. In the short follow-up (mean 3.9 years) cardiotoxicity is unlikely to have a role in the postoperative radiotherapy group. Theoretically, pulmonary damage (pneumonitis, fibrosis) may play a part since actual doses seem high. A relation with dose and treated volume is missing in the reviewed studies.Last, the BED2Munro AJ What now for postoperative radiotherapy for lung cancer?.Lancet. 1998; 352: 250-251Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar calculated for the PORT study does not take into account differences in overall treatment time. This omission enfeebles the suggestion of a relation between adverse effects of radiotherapy and BED. By applying the correction a more flattened BED-hazard ratio relation appears. We think that because of the accelerated proliferation of non-resected tumour cells and the length of the interval between surgery and radiotherapy, a total dose of 45 Gy is not sufficient to kill all tumour cells. Thus, we believe that it is not appropriate to draw conclusions for present day practice with linear accelerators and better treatment planning systems. The PORT investigators1PORT Meta-analysis Trialists GroupPostoperative radiotherapy in non-small cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials.Lancet. 1998; 352: 257-263Summary Full Text Full Text PDF PubMed Scopus (833) Google Scholar conclude that postoperative radiotherapy should not be routinely used to treat patients with completely resected early stage NSCLC. Alastair Munro2Munro AJ What now for postoperative radiotherapy for lung cancer?.Lancet. 1998; 352: 250-251Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar advises treatment of patients with a linear accelerator with a dose not greater than 45 Gy in 20 fractions (biological equivalent dose [BED] 79 Gy) or its biological equivalent. In addition, he states that another generation of trials is needed to address the issue of whether postoperative radiotherapy is beneficial or not. The role of postoperative radiotherapy in the treatment of patients with completely resected NSCLC is not yet established. However, a comparison with successful postoperative radiotherapy of, for example, mammary carcinoma forced itself to continue. We doubt whether a meta-analysis such as PORT can provide an answer to this relevant matter. We have several points to make. First, we think that it is not appropriate to refer to unpublished data. The reasons why these studies were not published in unknown. Second, it is inappropriate that patients excluded in the original published analyses were reinstated in the meta-analysis without justification of the reason for doing so. Third, no information is presented for the extent of mediastinal nodal resection. Improvement in survival has been shown when extensive surgical excision of mediastinal nodes is undertaken.3Emami B Management of hilar and mediastinal lymph nodes with radiation therapy in the treatment of lung cancer.in: Meyer J Frontiers in radiation therapy and oncology, vol 28. S Karger, Basel1994Google Scholar Fourth, treatment with cobalt is now judged obsolete, especially because of variations in dose. In only two studies was a linac used exclusively. In only two studies was a lung-factor correction applied (EORTC 08861; Lille). However, in the Lille trial dose was prescribed at the 90% isodose. Therefore actual lung doses were larger4Orton CG Chungbin S Klein EE Gillin MT Schultheiss TW Sause WT Study of lung density corrections in a clinical trial (RTOG 88–08).Int J Radiat Oncol Biol Phys. 1998; 41: 787-794Summary Full Text Full Text PDF PubMed Scopus (38) Google Scholar in 95% of all cases than noted in this analysis. Nor do the PORT investigators mention how patients who were assigned to postoperative radiotherapy but who did not actually receive radiotherapy were handled in the analysis. In our opinion, these patients should be excluded from further analysis. Fifth, causes of death other than cancer are not specified. In the short follow-up (mean 3.9 years) cardiotoxicity is unlikely to have a role in the postoperative radiotherapy group. Theoretically, pulmonary damage (pneumonitis, fibrosis) may play a part since actual doses seem high. A relation with dose and treated volume is missing in the reviewed studies. Last, the BED2Munro AJ What now for postoperative radiotherapy for lung cancer?.Lancet. 1998; 352: 250-251Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar calculated for the PORT study does not take into account differences in overall treatment time. This omission enfeebles the suggestion of a relation between adverse effects of radiotherapy and BED. By applying the correction a more flattened BED-hazard ratio relation appears. We think that because of the accelerated proliferation of non-resected tumour cells and the length of the interval between surgery and radiotherapy, a total dose of 45 Gy is not sufficient to kill all tumour cells. Thus, we believe that it is not appropriate to draw conclusions for present day practice with linear accelerators and better treatment planning systems. Postoperative radiotherapy in non-small-cell lung cancerAuthor's reply Full-Text PDF
In left-sided breast cancer radiotherapy, tangential intensity modulated radiotherapy combined with breath-hold enables a dose reduction to the heart and left anterior descending (LAD) coronary artery. Aim of this study was to investigate the added value of intensity modulated proton therapy (IMPT) with regard to decreasing the radiation dose to these structures.In this comparative planning study, four treatment plans were generated in 20 patients: an IMPT plan and a tangential IMRT plan, both with breath-hold and free-breathing. At least 97 % of the target volume had to be covered by at least 95 % of the prescribed dose in all cases. Specifically with respect to the heart, the LAD, and the target volumes, we analyzed the maximum doses, the mean doses, and the volumes receiving 5-30 Gy.As compared to IMRT, IMPT resulted in significant dose reductions to the heart and LAD-region even without breath-hold. In the majority of the IMPT cases, a reduction to almost zero to the heart and LAD-region was obtained. IMPT treatment plans yielded the lowest dose to the lungs.With IMPT the dose to the heart and LAD-region could be significantly decreased compared to tangential IMRT with breath-hold. The clinical relevance should be assessed individually based on the baseline risk of cardiac complications in combination with the dose to organs at risk. However, as IMPT for breast cancer is currently not widely available, IMPT should be reserved for patients remaining at high risk for major coronary events.
