title: Low-dose hyperradiosensitivity: is there a place for future investigation in clinical settings?
abstract: OBJECTIVE
  In vitro radiation doses of below 0.5 Gy have been shown to be more effective than higher doses per unit dose in killing clonogenic cells of many epithelial tumor cell lines. This phenomenon is known as low-dose hyperradiosensitivity. Preclinical studies have now suggested that there is synergism between chemotherapy and low-dose fractionated radiotherapy (LD-FRT). To test the clinical efficacy of this approach, we prospectively evaluated concurrent palliative chemotherapy and LD-FRT in patients with various types of epithelial tumors.
  
  
  METHODS
  Patients suffering from relapses or metastases of epithelial tumors were scheduled to receive concurrent LD-FRT (two fractions of 0.4 Gy per day) and chemotherapy. Radiologic assessments were performed after three cycles of chemotherapy plus LD-FRT.
  
  
  RESULTS
  Between June 2006 and October 2007, 12 patients with lung cancer, 7 patients with head-and-neck tumors, 2 patients with breast cancer, and 1 patient with esophageal carcinoma, for a total patient population of 22, underwent concomitant LD-FRT and chemotherapy. All patients but 3 (86%) had received previous treatments for their cancer. The median total dose of LD-FRT delivered was 800 cGy (range, 320-1280 cGy). The overall response rate was 45% (42% in previously treated patients). Grade 3-4 hematologic toxicities (Radiation Therapy Oncology Group ratings) were observed in 2 patients. At a median follow-up of 6.5 months, however, no local toxicity was observed.
  
  
  CONCLUSIONS
  In our experience, concurrent LD-FRT and chemotherapy was well tolerated. Because the response rate seems promising, prospective Phase II studies of the strategy are now under way.
authors.affiliation: Radiotherapy Department, Policlinico Universitario A.Gemelli, Catholic University, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
authors.forename: Mariangela
authors.initials: M
authors.lastname: Massaccesi
authors.forename: Mario
authors.initials: M
authors.lastname: Balducci
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mantini
authors.forename: Francesco
authors.initials: F
authors.lastname: Micciché
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Mattiucci
authors.forename: Nicola
authors.initials: N
authors.lastname: Dinapoli
authors.forename: Bruno
authors.initials: B
authors.lastname: Meduri
authors.forename: Giuseppe Roberto
authors.initials: GR
authors.lastname: D'Agostino
authors.forename: Giovanna
authors.initials: G
authors.lastname: Salvi
authors.forename: Luigia
authors.initials: L
authors.lastname: Nardone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy; D009369:Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D010166:Palliative Care / Q000379:methods*; D000068437:Pemetrexed; D011446:Prospective Studies; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D055815:Young Adult
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil