Locoregional recurrence after breast-conserving therapy remains an independent prognostic factor even after an event free interval of 10 years in early stage breast cancer
Breast-conserving therapy for early stage breast cancer has been a well-established therapeutic option for more than 30 years. Locoregional recurrence (LRR) after breast-conserving therapie has been proven to be a risk factor associated with an unfavourable long term outcome. Other significant long-term outcome prognostic factors as tumor size, nodal status or histological grade have been identified bevor, but their role decreases over time.
In this retrospective analysis the data of four randomised phase III clinical trials conducted by EORTC Breast Cancer Group and Radiotherapy Group were pooled in view of the role of LRR as an independent prognostic factor for overall survival (OS) and distant disease free survival (DFS). In total 7751 early stage breast cancer patients were included with a median follow up of 10.1 years. 910 of them suffered a LRR, most of them within ten years of primary diagnosis and treatment.
In the multivariate analysis of patients that had an event-free interval of at least 5 years LRR was the strongest independent prognostic factor for OF and DFS, in the group of patients event-free for more than ten years LRR was the only prognostic factor for DFS.
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Unilateral neck irradiation for well-lateralized oropharyngeal cancer
From January 2000 to June 2011 185 patients having a well-lateralized oropharyngeal cancer (T1-3N0-2b) were treated with unilateral neck irradiation. The treatment protocol was 46Gy (23 x 2 Gy, 6Fx/week) intensity-modulated radiotherapy to the ipsilateral neck in case of node negative disease. For node positive patients a neck dissection (ND) was performed after 46Gy of IMRT in the involved neck. The boost was preferentially applied with brachytherapy (22-Gy) or Cyberknife (3 x 5.5 Gy on consecutive days). Patients unsuitable for brachytherapy or Cyberknife boost were treated with 70-Gy of IMRT (additional 12 x 2 Gy, 6 fractions/week) to the primary tumor and the involved neck and did not undergo neck dissection .
Thirty events of treatment failure were reported: 6 regional failures, 16 local failures, and 8 distant failures. From six regional failures (3.2%) only two were contralateral (1.1%). All regional failures were successfully salvaged with surgery and postoperative radiotherapy, resulting in an regional control rate of 100%. 5-year disease free survival and overall survival were 84% and 70%.
The colleages from Rotterdam conclude that unilateral neck IMRT for well-lateralized oropharyngeal cancer showed excellent outcome and favorable toxicity profile.
Early Radiation Therapy in Atypical and Malignant Meningiomas
The WHO classification is correlated with prognosis and outcome of meningiomas.
High grade meningiomas (WHO °II + °III) are associated with aggressive local tumorgrowth, wherefore optimized local treatment options are nessesary. Adeberg and colleques analysed in a single institution trial the outcome of Radiotherapy in patients with high grade meningiomas (atypical: n=62; malignant: n=23). 60% received radiotherapy after surgical resection, 32 % in progression of desease and 8% in primary situation. GTV was defined as macroscopic leason/ resection cavity, adding 1-2cm margin for the CTV and another 1-5mm for the PTV. Patients treated with photon therapy received a median dose of 59,4 Gy.
The therapy was well tolerated with mild side effects.
5 year - OS correlates with the histological grading: 81% and 53% for atypical and anaplastic meningiomas, PFS after 5 years was 50% and 13%. The differences were significant (p=0,022 and p=0,017).
Radiotherapy, the target volume definition and dose is indicated in subject to the histological grading.
In malignant and atypical meningiomas early radiation after surgical resection increases PFS and OS. Intensity modulated Radiotherapy should be used for dose escalation in high grade meningiomas.
Evaluation of Mortality and Morbidity of Three Multimodality Regimes in Case of Stage IIIA Non-Small Cell Lung Cancer
In this retrospective assessment three multimodal treatment regimens for stage IIIA non-small cell lung cancer (NSCLC) have been analysed regarding morbidity and mortality. For definitive chemoradiation (D-CRT) concurrent chemoradiotherapy with a total up to a 60 Gy was performed. The trimodality-groups received 45 to 50,4 Gy (Tri-45) or >60 Gy (Tri-60) with concurrent chemoradiothrapy followed by resection.
In summary the treatment related morbidity and mortality rates for D-CRT were 74% [65 of 88] and 2,3% [2 of 88] whereas postoperative morbidity and mortality rates for Tri-45 and Tri-60 were 48% [27 of 57] and 1,8% [1 of 56], respectively. In conclusion neoadjuvant CRT was not associated with increased morbidity and mortality compared to definitive CRT - however the overall morbidity profile of chemoradiotherapy regardless of being definitive of neoadjuvant needs to be considered.
By VHan & FMan
Additional Use of Cetuximab in Patients with Oesophageal Cancer and Concurrent Chemoradiotherapy
In this multicentre randomized phase 2/3 trial 258 patients were recruited with non-metastatic, histologically confirmed carcinoma of oesophagus (WHO 0-1; Stage I-III disease). Patients were randomly assigned to receive definitive CRT alone or CRT with cetuximab (400mg/m² on day 1 and 250mg/m² weekly). CRT was composed of capecitabine 625mg/m² twice daily (d1-21) and cisplatin 60mg/m² (d1) for four cycles. Concomitantly radiotherapy with 50 Gy in 25 fractions within third and forth cycle was performed. In a nutshell fewer patients were treatment failure free in the CRT+ cetuximab-group and had a shorter median overall survival (22.1 month [95% CI 15.1 – 24.5] vs 25.4 month [20.5 – 37.9]; adj. HR 1.53 [95% CI 1.03-2.27]; p=0.035) compared with CRT alone. More non-haematological grade 3 or 4 toxicities were detected in the CRT + cetuximab-group. All in all addition of cetuximab to standard definitive CRT for patients with oesophageal cancer cannot be recommended.
By VHan & FMan
Surgery vs. Concurrent Radiochemotherapy – A Comparison in Case of Advanced Oropharyngeal Cancer
In this study the therapeutic outcome of surgery is compared with those of radiochemo therapy for patients with advanced oropharyngeal cancer using a matched-pair analysis. According to age, gender, subtide, and T and N classification finally 186 patients were matched between April 2005 to March 2007 by the Japan Clinical Oncology Group to underwent surgery or chemoradiation. The major endpoint was overall survival (OS). Additional endpoints were progression-free survival (PFS), local control rate (LCR) and swallowing function after initial therapy. 93 patients underwent surgery and 93 chemoradiation (with an median dose of 67Gy [range 60-72]) with additional chemotherapy. The statistical evaluation showed that in terms of 5-year OS, PFS and LCR there was no significant difference. The swallowing function was significant better in patients treated with chemoradiation than in those treated with surgery (p= 0.015). In summary this study showed that chemoradiation is as effective as surgery in the treatment of advanced oropharyngeal cancer and protects swallowing function significantly better.
By VHan & FMan
MR-Spectroscopy might help to define a boost volume for stereotactic radiotherapy in glioblastoma.
The optimal management of glioblastoma multiforme is still under ongoing investigation as the prognosis of this primary tumor of the brain is still poor (although some progress has been made). Usually the T1 contrast-enhancing region is considered as tumor in planning the radiotherapy, however a MRI-technique called “MR spectroscopy” (MRS) may be helpful to find areas of increased tumor-associated metabolic activity and thus might be helpful in better defining the tumor and a possible boost volume. Einstein and colleagues conducted a prospective Phase II trial where 35 patients where treated with a 15-25 Gy single fraction stereotactic boost to this MRS-positive region before starting fractionated radiotherapy (60 Gy à 2 Gy). Aprox. 50 % of the patients received temozolomide simultaneously.Grade 3-4 toxicities (including one stroke) occured in about 10% of patients.
Dependency of Colorectal Cancer on a TGF-β-Driven Program in Stromal Cells for Metastasis Initiation
The relevance of TGF-β signaling for disease progression is well known in tumors which retain a functional TGF-β pathway. However, around 40%-50% of all colorectal cancers (CRCs) exhibit mutational inactivation of TGF-β signaling pathway. Calon et al. investigated what CRCs gain from high TGF-β levels once the pathway is fully inactivated. They clearly showed that TGF-β secreted by CRCs into the microenvironment of the tumor activated a TGF-β responsive pathway in stromal cells that is associated with a significant higher risk of CRC relapse. Patients with low TGFB expression levels in their primary tumor remained mostly disease-free during a 10 years follow up study. Therefore, high TGF-β levels are robust predictors for disease relapse. In in vivo mice models, inhibition of TGF-β stromal signaling prevented metastasis initiation but not tumor growth. Hence, the success of pharmacological blockade of TGF-β signaling in order to prevent relapse of the disease and metastasis formation in terms of clinical purposes remains questionable.
Keywords: TGF-β signaling, colorectal cancer, stroma, metastasis, relapse
Short-term versus long-term hormone therapy plus radiotherapy or prostatectomy for prostate cancer: a systematic review and meta-analysis
This meta-analysis investigated 9 randomized controlled trial to compare the efficacy of short term HAT (duration < 6 mo) versus long term HAT (duration > 6 mo) plus radiotherapy (RT) or prostatectomy (RP).
RT + short-term HAT vs RT + long-term HAT (7 trials):
There was no difference in OS and DFS between short-term and long-term HAT, but long-term HAT showed a trend towards improved OS. Clinical progression rate, the rate of biochemical failure and prostate cancer-specific mortality was significantly higher in the short-term HAT group. There were discrepant results of adverse events.
RP + short term HAT vs RP + long-term HAT (2 trials):
Long-term HAT was superior to short-term HAT in positive surgical margin rate and prostate volume before RP. There was no significant difference in PSA level before RP between the two groups. The results of longer follow-up time were absent.
Conclusion: Long-term HAT may have a greater benefit, but showed no improved OS and the adverse reactions are inevitable.
Neoadjuvant Chemotherapy in patients with breast cancer: Predictors of Locoregional Recurrence: NSABP B18+27
A smal number of patients with operable breast cancer receive neoadjuvant chemotherapy. So there is limited information on rates and predictors of locoregional recurrence (LRR) in these patients. Eleftherios and colleques analysed the results of following two trials including 3088 patients with breast cancer (T1-3 N0-1M0) receiving neoadjuvant chemotherapy between 1988 and 2000:
1. NSABP B-18: 742 patients undergoing 4 cycles of AC
2. NSABP B-27: 2346 (in 3 groups) patients were treated with 4 x AC neoadjuvant +/- 4x Docetaxel präoperative or postoperative
In both studies, patients undergoing lumpectomy received radiation therapy, patients treated with mastectomy received no radiation. The median follow up was 12 years:
Patients in the neoadjuvant CHX arms had LRR rates of 12,6% and 10,3 % (mastectomy vs. lumpectomy + RT) after 10 years. Significant independent factors of LRR were tumor size and clinical nodal status before therapy and pathological nodal status/breast tumor response and age (only in patients receiving RT).
The risk of LRR is althought increased with increasing number of positive nodes after neoadjuvant chemotherapy.
These informations can be used for predicting risk of LRR and for indicating the optimal use of RT after neoadjuvant chemotherapy.