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
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.
Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy.
In a retrospective analysis the Department of Surgery of the Memorial Sloan-Kettering Cancer Center evaluated the controversial discussed nonoperative management (NOM) of rectal cancer after a complete clinical response (cCR) to neoadjuvant therapy as a promising treatment option for stage I to III rectal cancer. 32 patients which were treated by NOM after completing neoadjuvant CRT and cCR were compared to 57 patients with pCR after neoadjuvant CRT and rectal resection. There was no local recurrence in the surgery group; 6 local failures in the NOM-group were controlled by salvage rectal resection with no further local recurrence of disease, so rectal resection was successfully avoided in 81% of patients in the NOM-group. NOM combined with salvage surgery achieved similar local and distant disease control. However prospective trials are needed to verify these results.
Keywords: complete clinical response, neoadjuvant therapy, rectal cancer
Hyperfractionated versus conventional radiotherapy in standard-risk medulloblastoma
The results from the randomized multicenter HIT-SIOP-PNET 4 Trial are presented. 344 children from 122 different European centers were postoperatively staged and randomly assigned to treatment with hyperfractionated radiotherapy (HFRT= 36,0Gy craniospinal+ 24,0Gy cerebellum + 8,0Gy boost tumorregion; 68,0Gy total dose; 2x1,0Gy/daily) or conventional fractionated radiotherapy (CFRT= 23,4 Gy craniospinal + 30,6 Gy cerebellum; 54,0Gy total dose; 1,8Gy/daily) followed by chemotherapy with CCNU, Cisplatin and Vincristin.
After a median follow-up of 4,8 years, survival rates were similar in both treatment groups. A postoperative residual tumor >1,5cm and a delay of more than 7 weeks to the start of the RT had a worse prognosis. Severe hearing loss was not significantly different.
The final data about neurocognitive toxicity are not presented. Till these data are available, a conventional fractionated radiotherapy is standard and admissible.
Note: according to other smaller studies (Carrie 2009 and Gupta 2012), children who received HFRT had better executive function than children in CFRT.
Single dose of carboplatin is not inferior to radiotherapy in Stage I seminoma
Stage I seminoma is the most common testicular germ cell tumor; Radiotherapy used to play a central role in the treatment of this highly curable malignancy. Treatment strategies after orchiectomie now are surveillance, adjuvant radiotherapy or chemotherapy (carboplatin);
To compare the latter two strategies, a non-inferiority trial has been conducted; almost 1500 patients were randomly assigned to either a single dose carboplatin (AUC7) infusion or radiotherapy (20-30 Gy).
Oliver and colleagues now present the 6,5 year follow-up data of this trial confirming the non-inferiority of carboplatin to radiation therapy; relapse-free survival was comparable in both groups (Chx 95% vs RT 96%); In the chemotherapy group, less side-effects have been reported. Interestingly, the use of carboplatin also reduced the risk of contralateral germ cell tumors.
In conclusion, adjuvant chemotherapy is a valid alternative to adjuvant radiotherapy in stage I seminoma.
In the recent guidelines by the European germ cell consensus group, surveillance is recommended in most (low risk) cases as 88% of the patients are cured by orchiectomie alone. In case of a relapse, rates of curation are still high.
#seminoma #radiotherapy #chemotherapy #LMU
Escalated radiation dose alone vs. concurrent chemoradiation for locally advanced and unresectable rectal cancer: results from phase II randomized study
Aim of this trial was to determine whether neoadjuvant concurrent chemoradiation or boosted radiotherapy alone results in a higher resectability rate in patients with initially unresectable rectal adenocarcinoma.
Patients were randomized either to receive external beam radiotherapy (EBRT) to the pelvis (45Gy/1.8Gy) with concurrent oral Capecitabine (1,700mg/m²; d1-14 & d22-35) (CRT group; Arm 1; n= 46 pat.) or EBRT to the pelvis (45Gy/1.8Gy) alone followed by a localized radiotherapy boost (20Gy/2Gy) to the primary tumor site (RT with boost group; Arm 2; n= 44 pat.). Resectability was then evaluated by CT scan 6 – 8 weeks later. Only 40 patients, who then seemed to be resectable, underwent operation. No exenterations were performed.
Resectability rates were low in both arms: R0-resection was achieved in 20 (43%) patients in Arm 1 vs. 15 (34%) patients in Arm 2 (p>0,05). Factors, that significantly affected resectability in both groups were extension of tumor to pelvic bones and signet ring cell pathology. Complete pathological control was seen in 7% in Arm 1 and in 11% in Arm 2. There was significantly greater postoperative morbidity in Arm 2 (16 vs. 40%), though acute toxicity was comparably the same in both groups.
Neoadjuvant escalated dose radiation, compared with neoadjuvant chemoradiation did not result in higher complete R0 tumor resectability in locally advanced inoperable rectal cancer.
More studies need to be undertaken to address the question of preoperative dose escalation with IMRT technique and of more aggressive preoperative chemotherapy in advanced rectal cancers.