Postmastectomy radiotherapy in T1-2 patients with one to three positive lymph nodes - Past, present and future.

PAST: The role of post-mastectomy radiotherapy (PMRT) in patients with tumor <5 cm and one to three positive lymph nodes after axillary dissection (ALND) is vigorously debated. Initial doubts over the efficacy and safety of PMRT in these patients were partially overcome by improvement in technology and systemic treatments. Several randomized controlled clinical trials confirmed benefit of PMRT in N1 patients, which were meta-analyzed by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG). This meta-analysis provides the sole high-level evidence to guide clinical decision-making. PRESENT: Nevertheless, concerns have been evoked around these results, most notably concerning the patient selection bias and the era in which the patients were treated. More recent studies, albeit retrospective, are in contrast with this level I evidence, unequivocally reporting inferior recurrence rates in control arms than those of the EBCTCG meta-analysis. Taken together, these results suggest that one solution would not fit all N1 patients and that patient selection for PMRT shall be stratified upon risks factors. Most prominent of such factors identified are: patient age; number and ratio of positive lymph nodes; histological features such as lymphovascular invasion; and hormone receptor expression. FUTURE: A prospective randomized controlled trial SUPREMO will release its final results in 2023 and shed light onto the subject. Genomic tumor cell profiling will likely provide further guidelines in terms of risk stratification. SUPREMO translational sub-study will also offer material for genomic analyses. A cross-field tendency to forgo nodal dissection in favor of sentinel lymph node biopsy followed by nodal irradiation might eventually render the question of PMRT indication after ALND irrelevant.

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.

Genomic classifications and radiotherapy for breast cancer.

The current therapeutic strategy in breast cancer rests on standard prognostic factors such as size, histological grade, nodal and hormone receptor status. However, over the last decade, a new form of molecular classification has emerged to complement the classical clinico-pathological staging. Models based on tumour genome have been developped to help predict the risk of relapse, and are currently being evaluated. This improved risk stratification tool would enable the identification of patients who would benefit from systemic as well as local treatments. This paper aims to give an overview of the radiobiological implications in particular of this new classification, by looking at on the one hand, predictors of local relaspe, and on the other hand, the modulation in radiotherapy according to molecular type.

Performance of 18F-fluoro-ethyl-tyrosine (18F-FET) PET for the differential diagnosis of primary brain tumor: a systematic review and Metaanalysis.

UNLABELLED: For the past decade, PET with (18)F-fluoro-ethyl-tyrosine ((18)F-FET) has been used in the evaluation of patients with primary brain tumors (PBTs), but so far series have reported only a limited number of patients. The purpose of this systematic review and metaanalysis was to assess the diagnostic performance of (18)F-FET PET in patients with suspicion of PBT. METHODS: We examined studies published in the literature using MEDLINE and EMBASE databases. Inclusion criteria were use of (18)F-FET PET for initial assessment of patients with a newly diagnosed brain lesion; patients who had no radiotherapy, surgery, or chemotherapy before (18)F-FET PET; and use of histology as a gold standard. Metaanalysis was performed on a per-patient basis. We secondarily performed receiver-operating-characteristic analysis of pooled patients to determine tumor-to-background ratio (TBR) of (18)F-FET uptake and best diagnostic value. RESULTS: Thirteen studies totaling 462 patients were included. For the diagnosis of PBT, (18)F-FET PET demonstrated a pooled sensitivity of 0.82 (95% confidence interval [CI], 0.74-0.88), specificity of 0.76 (95% CI, 0.44-0.92), area under the curve of 0.84 (95% CI, 0.80-0.87), positive likelihood ratio of 3.4 (95% CI, 1.2-9.5), and negative likelihood ratio of 0.24 (95% CI, 0.14-0.39). Receiver-operating-characteristic analysis indicated that a mean TBR threshold of at least 1.6 and a maximum TBR of at least 2.1 had the best diagnostic value for differentiating PBTs from nontumoral lesions. CONCLUSION: (18)F-FET PET demonstrated excellent performance for diagnosing PBTs. Strict standardization of PET acquisition protocols and prospective, multicenter studies investigating the added value over current MRI are now needed to establish (18)F-FET PET as a highly relevant tool for patient management.

Higher toxicity with 42 Gy in 10 fractions as a total dose for 3D-conformal accelerated partial breast irradiation: results from a dose escalation phase II trial.

OBJECTIVE: Recent recommendations regarding indications of accelerated partial breast irradiation (APBI) have been put forward for selected breast cancer (BC) patients. However, some treatment planning parameters, such as total dose, are not yet well defined. The Institut Gustave Roussy has initiated a dose escalation trial at the 40 Gy/10 fractions/5 days and at a further step of total dose (TD) of 42 Gy/10 fractions/ 5 days. Here, we report early results of the latest step compared with the 40 Gy dose level. METHODS AND MATERIALS: From October 2007 to March 2010, a total of 48 pT1N0 BC patients were enrolled within this clinical trial: 17 patients at a TD of 42 Gy/10f/5d and 31 at a TD of 40 Gy/10f/5d. Median follow-up was 19 months (min-max, 12-26). All the patients were treated by APBI using a technique with 2 minitangents and an "enface" electrons delivering 20% of the total dose. Toxicities were systematically assessed at 1; 2; 6 months and then every 6 months. RESULTS: Patients' recruitment of 42 Gy step was ended owing to persistent grade 3 toxicity 6 months after APBI completion (n = 1). Early toxicities were statistically higher after a total dose of 42 Gy regarding grade ≥2 dry (p = 0.01) and moist (p = 0.05) skin desquamation. Breast pain was also statistically higher in the 42 Gy step compared to 40 Gy step (p = 0.02). Other late toxicities (grade ≥2 fibrosis and telangectasia) were not statistically different between 42 Gy and 40 Gy. CONCLUSIONS: Early toxicities were more severe and higher rates of late toxicities were observed after 42 Gy/10 fractions/5 days when compared to 40 Gy/10 fractions/5 days. This data suggest that 40 Gy/10 fractions/ 5 days could potentially be the maximum tolerance for PBI although longer follow-up is warranted to better assess late toxicities.

Low-dose radiotherapy in indolent lymphoma.

PURPOSE: To assess the response rate, duration of response, and overall survival after low-dose involved-field radiotherapy in patients with recurrent low-grade lymphoma or chronic lymphocytic leukemia (CLL). METHODS AND MATERIALS: Forty-three (24 women, 19 men) consecutive patients with indolent lymphoma or CLL were treated with a total dose of 4 Gy (2 × 2 Gy) using 6- 18-MV photons. The median age was 73 years (range, 39-88). Radiotherapy was given either after (n = 32; 75%) or before (n = 11; 25%) chemotherapy. The median time from diagnosis was 48 months (range, 1-249). The median follow-up period was 20 months (range, 1-56). RESULTS: The overall response rate was 90%. Twelve patients (28%) had a complete response, 15 (35%) had a partial response, 11 (26%) had stable disease, and 5 (11%) had progressive disease. The median overall survival for patients with a positive response (complete response/partial response/stable disease) was 41 months; for patients with progressive disease it was 6 months (p = 0.001). The median time to in-field progression was 21 months (range, 0-24), and the median time to out-field progression was 8 months (range, 0-40). The 3-year in-field control was 92% in patients with complete response (median was not reached). The median time to in-field progression was 9 months (range, 0.5-24) in patients with partial response and 6 months (range, 0.6-6) in those with stable disease (p < 0.05). Younger age, positive response to radiotherapy, and no previous chemotherapy were the best factors influencing the outcome. CONCLUSIONS: Low-dose involved-field radiotherapy is an effective treatment in the management of patients with recurrent low-grade lymphoma or CLL.