Radiation dose intensification in pre-operative chemo-radiotherapy for locally advanced rectal cancer.
BACKGROUND
To assess the role of radiation dose intensification with simultaneous integrated boost guided by 18-FDG-PET/CT in pre-operative chemo-radiotherapy (ChT-RT) for locally advanced rectal cancer.


METHODS
A prospective study was approved by the Internal Review Board. Inclusion criteria were: age >18 years old, World Health Organization performance status of 0-1, locally advanced histologically proven adenocarcinoma of the rectum within 10 cm of the anal verge, signed specific informed consent. High-dose volumes were defined including the hyper-metabolic areas of 18-FDG-PET/CT of primary tumor and the corresponding mesorectum and/or pelvic nodes with at least a standardized uptake values (SUV) of 5. A dose of 60 Gy/30 fractions was delivered. A total dose of 54 Gy/30 fractions was delivered to prophylactic areas. Capecitabine was administered concomitantly with RT for a dose of 825 mg/mq twice daily for 5 days/every week.


RESULTS
Between September 2011 and July 2015 fortypatients were recruited. At the time of the analysis, median follow up was 20 months (range 5-51). The median interval from the end of ChT-RT to surgery was 9 weeks (range 8-12). Thirty-seven patients (92.5 %) were submitted to sphincter preservation. Tumor Regression Grade (Mandard scale) was recorded as follows: grade 1 in 7 (17.5 %), grade 2 in 17 (42.5 %), grade 3 in 15 (37.5 %) and grade 4 in 1 (2.5 %). Post-surgical circumferential resection margin was negative in all patients. A tumor downstaging was reported in 62.5 % (95 % CI: 0.78-0.47). A nodes downstaging was registered in 85 % (95 % CI: 0.55-0.25). 18-FDG-PET/CT was not able to predict pCR. No correlation was found between pre-treatment SUV-max values and pCR. A metabolic tumor volume >127 cc was related to ypT ≥2 (p 0.01). Patients with TRG >2 had higher tumor lesion glycolysis values (p 0.05).


CONCLUSIONS
Preliminary results did not confirm some advantages in terms of primary tumor downstaging/downsizing compared to conventional schedules reported in historical series. The role of 18-FDG-PET/CT in neoadjuvant rectal cancer management needs to be confirmed in further investigations. Long terms results are necessary.
Radiation Oncology Division, Sacro Cuore Don Calabria Cancer Care Center, Negrar, Verona, Italy.
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Alongi
Radiation Oncology Division, Sacro Cuore Don Calabria Cancer Care Center, Negrar, Verona, Italy.
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Fersino
Radiation Oncology Division, Sacro Cuore Don Calabria Cancer Care Center, Negrar, Verona, Italy. rosariomazzola@hotmail.it.
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Mazzola
Radiation Oncology Division, Sacro Cuore Don Calabria Cancer Care Center, Negrar, Verona, Italy.
A
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Fiorentino
Radiation Oncology Division, Sacro Cuore Don Calabria Cancer Care Center, Negrar, Verona, Italy.
N
N
Giaj-Levra
Radiation Oncology Division, Sacro Cuore Don Calabria Cancer Care Center, Negrar, Verona, Italy.
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Ricchetti
Radiation Oncology Division, Sacro Cuore Don Calabria Cancer Care Center, Negrar, Verona, Italy.
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Ruggieri
Statistic Science Faculty, University of Palermo, Palermo, Italy.
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Di Paola
Medical Oncology Division, Sacro Cuore Don Calabria Cancer Care Center, Negrar, Verona, Italy.
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M
Cirillo
Medical Oncology Division, Sacro Cuore Don Calabria Cancer Care Center, Negrar, Verona, Italy.
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Gori
Nuclear Medicine Division, Sacro Cuore Don Calabria Cancer Care Center, Negrar, Verona, Italy.
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Salgarello
Pathology Division, Sacro Cuore Don Calabria Cancer Care Center, Negrar, Verona, Italy.
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Zamboni
Surgery Division, Sacro Cuore Don Calabria Cancer Care Center, Negrar, Verona, Italy.
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Ruffo
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000072078:Positron Emission Tomography Computed Tomography; D011300:Preoperative Care; D011379:Prognosis; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
Dose intensification; Rectal cancer; Simultaneous integrated boost; Volumetric modulated arc therapy