- Email: [email protected]
SP-0145: Surgery in squamous cell cancer of the anus
S56 9
University Hospital of Vall d'Hebron, Institute of Oncology-VHIO, Barcelona, Spain Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus, Denmark
10
Purpose/Objective: ATM plays a key role in the detection of DNA double strand breaks and initiation of downstream processes that lead to cell cycle arrest, DNA repair or apoptosis. A number of smaller clinical studies have indicated that the ATM codon 1853 Asp/Asn SNP may be linked to normal tissue toxicity risk. Nevertheless, as for many other SNPs, the results have been conflicting and difficult to interpret. The present study was conducted to bring this SNP to a test in the setting of a well-powered multicentre meta-analysis. Materials and Methods: Within the framework of the International Radiogenomics Consortium, published as well as unpublished individual patient data were collected from 17 different study cohorts. The dataset comprised more than 190,000 individual toxicity recordings after radiotherapy in 2779 patients with prostate cancer and 2655 patients with breast cancer. To compare toxicity scores across different endpoints, grading systems and institutions, all toxicity recordings were converted into z-scores. Based on these z-scores, STAT-scores (1) were calculated for overall toxicity (n=5304), acute toxicity (n=2322) and late toxicity (n=5023). Furthermore, z-scores were calculated for acute skin toxicity (n=1357), telangiectasia (n=1654), subcutaneous fibrosis (n=2291) and late proctitis (n=2215). STAT or z-scores for these 7 endpoints were compared for patients with different ATM codon 1853 genotypes. Results: Using a t-test comparing the Asp/Asn and Asn/Asn genotypes with the Asp/Asp genotype, a small but significant increase in normal tissue radio responsiveness was found for patients having one or two Asn alleles with regard to STAT scores for acute toxicity (p=0.001), late toxicity (p=0.029) and overall toxicity (p=0.003) as well as for the z scores for acute skin toxicity (p=0.001) and telangiectasia (p=0.003). Using a Spearman correlation test (that takes all three possible genotypes into account), significant correlations with the Asn allele were found for STAT acute (p=0.001), STAT overall (p=0.002) and z acute skin (p=0.001). The findings were consistent with a co-dominant / additive pattern of inheritance. We finally calculated odds for having a STAT or zscore in the upper quartile for patients with Asp/Asn or Asn/Asn vs. Asp/Asp genotype (figure 1).
This indicates an odds ratio of around 1.2 for late toxicity and around 1.5 for acute toxicity. Only the results for z acute skin, STAT acute and STAT overall reached statistical significance in this analysis. Conclusions: This study, by far the largest of its kind, demonstrated a small but significant impact of the ATM codon 1853 Asn allele upon normal tissue radiosensitivity. The influence seems to be stronger for acute than for late toxicity. The effect size is in the order of magnitude that should be expected for SNPs. 1) Barnett GC et al. IJROBP (2012) 1;82(3):1065-74
JOINT SYMPOSIUM: ESTRO-ESMO-ESSO: GUIDELINES ON ANAL CANAL CANCEr SP-0144 Introducing the ESMO-ESTRO-ESSO clinical guideline on anal cancer C. Belka1 1 Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Department of Radiation Oncology, München, Germany Today, effective treatment of merely all cancer entities relies on the perfect interaction of different medical subspecialities. In contrast
ESTRO 33, 2014 to past approaches were cancer treatment strategies were guided mainly by "first see - frist decide" principles, nowadays evidence derived from clinical trials directs treatment decisions. In this regard, guidelines prepared by representatives from all involved medical subspeialities are of crucial importance. These guidelines provide a stable - and best evidence based - framework for clincal decisions. Nevertheless these guidelines only provide a framework for clinical decision and will never replace individual judgements. In order to adequately manage the preparation, release and endorsment of clinical guidelines ESTRO has recently introduced the ARCOP (Advisory Committee on Radiation Oncology Practice) committee which was already involved in the generation of the given anal cancer guideline. In case of anal cancer, an multitude of clinical trial have provided strong evidence that radiochemotherapy based approaches currently represent the most suitable approach for cancer control and maintenance of function. The new ESMO-ESTRO-ESSO guideline will be presented in the following session. SP-0145 Surgery in squamous cell cancer of the anus P.J. Nilsson1 1 Karolinska University Hospital, Division of Coloproctology Center of Surgical Gastroenterology P9:03, Stockholm, Sweden The role of surgery in treatment of squamous cell cancer (SCCA) of the anus has dramatically changed since the landmark reports on definitive chemoradiation from the 1970’s. Despite this, surgery and the colorectal surgeon are still key players in the multidisciplinary management of SCCA. Following adequate staging, which should include clinical assessment and proctoscopy (if needed under general anaesthesia), magnetic resonance imaging of the pelvis and exclusion of distant metastasis (preferably by a PET/CT), SCCA patients should be discussed at a multidisciplinary team (MDT) board. A vast majority of patients should be suggested primary non-surgical therapy. In some instances, e.g. tumour fistulating into vagina, a pre-treatment stoma should be considered although these stomas are rarely closed. Only in smaller lesions (< 2cm) that are not poorly differentiated and only involving the anal margin, primary surgery (local excision) is a valid option, provided adequate margins without compromise of sphincter function can be obtained. Primary abdominoperineal excision (APE) is an option in patients previously irradiated to the pelvis or, more uncommon, on patient preference. Patients with locally persistent, progressive or recurrent disease after chemoradiation should be assessed for salvage surgery. In only a very small proportion of these patients local excision is a valid alternative and at least an APE is mandated. Since achievement of negative resection margins is crucial, a posterior or total pelvic exenteration may be required in a proportion of patients. Thus, surgery should preferably be carried out in institutions experienced in multi-visceral excisions. Again, careful staging pre-operatively is mandatory to plan adequate operative strategy but also to exclude patients in whom surgery would be futile. Persistent or progressive disease in inguinal lymph nodes should be considered for surgery and, more seldom, also distant metastasis may be candidates for operative treatment following a MDT decision. Because of the nature of SCCA and treatment prior to salvage surgery, the operative technique differs somewhat from that used in rectal cancer surgery. Salvage surgery in SCCA involves wide resections in heavily irradiated tissue and is connected with a high risk of postoperative complications. In particular, the perineal wound is associated with a substantial risk of post-operative morbidity. The use of musculocutaneous flaps for perineal reconstruction is recommended to reduce this risk. Salvage surgery in SCCA can achieve local pelvic control in approximately 60% of patients and 5-year survival rates ranging from 30% to over 60% have been reported. SP-0146 New concepts for radiotherapy in anal canal cancers P.M. Maingon1 1 Centre Georges-François Leclerc, Radiotherapy, Dijon, France In the field of anal carcinoma, much progress has been made over the past few decades in the diagnosis and the management of cancer of the anal canal. Firstly, the diagnosis procedure dramatically improve with the systematic use of PET CT and MRI, aiming to determine more precisely the tumor size, it extend to the lymph nodes, providing useful tools for the delineation of the target volumes. More, this procedure demonstrated their usefulness during the follow-up of the patient under certain conditions. During the same period, integration of alternative chemotherapy regimens and the use of intensity modulated radiation therapy (IMRT) with new combined modality therapy (CRT) have been tested to improve
University Hospital of Vall d'Hebron, Institute of Oncology-VHIO, Barcelona, Spain Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus, Denmark
10
Purpose/Objective: ATM plays a key role in the detection of DNA double strand breaks and initiation of downstream processes that lead to cell cycle arrest, DNA repair or apoptosis. A number of smaller clinical studies have indicated that the ATM codon 1853 Asp/Asn SNP may be linked to normal tissue toxicity risk. Nevertheless, as for many other SNPs, the results have been conflicting and difficult to interpret. The present study was conducted to bring this SNP to a test in the setting of a well-powered multicentre meta-analysis. Materials and Methods: Within the framework of the International Radiogenomics Consortium, published as well as unpublished individual patient data were collected from 17 different study cohorts. The dataset comprised more than 190,000 individual toxicity recordings after radiotherapy in 2779 patients with prostate cancer and 2655 patients with breast cancer. To compare toxicity scores across different endpoints, grading systems and institutions, all toxicity recordings were converted into z-scores. Based on these z-scores, STAT-scores (1) were calculated for overall toxicity (n=5304), acute toxicity (n=2322) and late toxicity (n=5023). Furthermore, z-scores were calculated for acute skin toxicity (n=1357), telangiectasia (n=1654), subcutaneous fibrosis (n=2291) and late proctitis (n=2215). STAT or z-scores for these 7 endpoints were compared for patients with different ATM codon 1853 genotypes. Results: Using a t-test comparing the Asp/Asn and Asn/Asn genotypes with the Asp/Asp genotype, a small but significant increase in normal tissue radio responsiveness was found for patients having one or two Asn alleles with regard to STAT scores for acute toxicity (p=0.001), late toxicity (p=0.029) and overall toxicity (p=0.003) as well as for the z scores for acute skin toxicity (p=0.001) and telangiectasia (p=0.003). Using a Spearman correlation test (that takes all three possible genotypes into account), significant correlations with the Asn allele were found for STAT acute (p=0.001), STAT overall (p=0.002) and z acute skin (p=0.001). The findings were consistent with a co-dominant / additive pattern of inheritance. We finally calculated odds for having a STAT or zscore in the upper quartile for patients with Asp/Asn or Asn/Asn vs. Asp/Asp genotype (figure 1).
This indicates an odds ratio of around 1.2 for late toxicity and around 1.5 for acute toxicity. Only the results for z acute skin, STAT acute and STAT overall reached statistical significance in this analysis. Conclusions: This study, by far the largest of its kind, demonstrated a small but significant impact of the ATM codon 1853 Asn allele upon normal tissue radiosensitivity. The influence seems to be stronger for acute than for late toxicity. The effect size is in the order of magnitude that should be expected for SNPs. 1) Barnett GC et al. IJROBP (2012) 1;82(3):1065-74
JOINT SYMPOSIUM: ESTRO-ESMO-ESSO: GUIDELINES ON ANAL CANAL CANCEr SP-0144 Introducing the ESMO-ESTRO-ESSO clinical guideline on anal cancer C. Belka1 1 Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Department of Radiation Oncology, München, Germany Today, effective treatment of merely all cancer entities relies on the perfect interaction of different medical subspecialities. In contrast
ESTRO 33, 2014 to past approaches were cancer treatment strategies were guided mainly by "first see - frist decide" principles, nowadays evidence derived from clinical trials directs treatment decisions. In this regard, guidelines prepared by representatives from all involved medical subspeialities are of crucial importance. These guidelines provide a stable - and best evidence based - framework for clincal decisions. Nevertheless these guidelines only provide a framework for clinical decision and will never replace individual judgements. In order to adequately manage the preparation, release and endorsment of clinical guidelines ESTRO has recently introduced the ARCOP (Advisory Committee on Radiation Oncology Practice) committee which was already involved in the generation of the given anal cancer guideline. In case of anal cancer, an multitude of clinical trial have provided strong evidence that radiochemotherapy based approaches currently represent the most suitable approach for cancer control and maintenance of function. The new ESMO-ESTRO-ESSO guideline will be presented in the following session. SP-0145 Surgery in squamous cell cancer of the anus P.J. Nilsson1 1 Karolinska University Hospital, Division of Coloproctology Center of Surgical Gastroenterology P9:03, Stockholm, Sweden The role of surgery in treatment of squamous cell cancer (SCCA) of the anus has dramatically changed since the landmark reports on definitive chemoradiation from the 1970’s. Despite this, surgery and the colorectal surgeon are still key players in the multidisciplinary management of SCCA. Following adequate staging, which should include clinical assessment and proctoscopy (if needed under general anaesthesia), magnetic resonance imaging of the pelvis and exclusion of distant metastasis (preferably by a PET/CT), SCCA patients should be discussed at a multidisciplinary team (MDT) board. A vast majority of patients should be suggested primary non-surgical therapy. In some instances, e.g. tumour fistulating into vagina, a pre-treatment stoma should be considered although these stomas are rarely closed. Only in smaller lesions (< 2cm) that are not poorly differentiated and only involving the anal margin, primary surgery (local excision) is a valid option, provided adequate margins without compromise of sphincter function can be obtained. Primary abdominoperineal excision (APE) is an option in patients previously irradiated to the pelvis or, more uncommon, on patient preference. Patients with locally persistent, progressive or recurrent disease after chemoradiation should be assessed for salvage surgery. In only a very small proportion of these patients local excision is a valid alternative and at least an APE is mandated. Since achievement of negative resection margins is crucial, a posterior or total pelvic exenteration may be required in a proportion of patients. Thus, surgery should preferably be carried out in institutions experienced in multi-visceral excisions. Again, careful staging pre-operatively is mandatory to plan adequate operative strategy but also to exclude patients in whom surgery would be futile. Persistent or progressive disease in inguinal lymph nodes should be considered for surgery and, more seldom, also distant metastasis may be candidates for operative treatment following a MDT decision. Because of the nature of SCCA and treatment prior to salvage surgery, the operative technique differs somewhat from that used in rectal cancer surgery. Salvage surgery in SCCA involves wide resections in heavily irradiated tissue and is connected with a high risk of postoperative complications. In particular, the perineal wound is associated with a substantial risk of post-operative morbidity. The use of musculocutaneous flaps for perineal reconstruction is recommended to reduce this risk. Salvage surgery in SCCA can achieve local pelvic control in approximately 60% of patients and 5-year survival rates ranging from 30% to over 60% have been reported. SP-0146 New concepts for radiotherapy in anal canal cancers P.M. Maingon1 1 Centre Georges-François Leclerc, Radiotherapy, Dijon, France In the field of anal carcinoma, much progress has been made over the past few decades in the diagnosis and the management of cancer of the anal canal. Firstly, the diagnosis procedure dramatically improve with the systematic use of PET CT and MRI, aiming to determine more precisely the tumor size, it extend to the lymph nodes, providing useful tools for the delineation of the target volumes. More, this procedure demonstrated their usefulness during the follow-up of the patient under certain conditions. During the same period, integration of alternative chemotherapy regimens and the use of intensity modulated radiation therapy (IMRT) with new combined modality therapy (CRT) have been tested to improve