Predictors of acute toxicities during definitive chemoradiation using intensity-modulated radiotherapy for anal squamous cell carcinoma

Abstract

Purpose To identify clinical and dosimetric factors associated with acute hematologic and gastrointestinal (GI) toxicities during definitive therapy using intensity-modulated radiotherapy (IMRT) for anal squamous cell carcinoma (ASCC). Materials and methods We retrospectively analyzed 108 ASCC patients treated with IMRT. Clinical information included age, gender, stage, concurrent chemotherapy, mitomycin (MMC) chemotherapy and weekly hematologic and GI toxicity during IMRT. From contours of the bony pelvis and bowel, dose-volume parameters were extracted. Logistic regression models were used to test associations between toxicities and clinical or dosimetric predictors. Results The median age was 59 years, 81 patients were women and 84 patients received concurrent MMC and 5-fluorouracil (5FU). On multivariate analysis (MVA), the model most predictive of Grade 2 + anemia included the maximum bony pelvis dose (Dmax), female gender, and T stage [p = 0.035, cross validation area under the curve (cvAUC) = 0.66]. The strongest model of Grade 2 + leukopenia included V10 (percentage of pelvic bone volume receiving ≥ 10 Gy) and number of MMC cycles (p = 0.276, cvAUC = 0.57). The model including MMC cycle number and T stage correlated best with Grade 2 + neutropenia (p = 0.306, cvAUC = 0.57). The model predictive of combined Grade 2 + hematologic toxicity (HT) included V10 and T stage (p = 0.016, cvAUC = 0.66). A model including VA45 (absolute bowel volume receiving ≥ 45 Gy) and MOH5 (mean dose to hottest 5% of bowel volume) best predicted diarrhea (p = 0.517, cvAUC = 0.56). Conclusion Dosimetric constraints to the pelvic bones should be integrated into IMRT planning to reduce toxicity, potentially reducing treatment interruptions and improving disease outcomes in ASCC. Specifically, our results indicate that Dmax should be confined to ≤ 57 Gy to minimize anemia and that V10 should be restricted to ≤ 87% to reduce incidence of all HT.

Late gastrointestinal toxicity after radiotherapy for anal cancer: a systematic literature review

“…Studies reporting the long-term outcome of IMRT reported either no or very rare incidence of Grade 3 or higher late sequelae [14,58,61,97,98,[129][130][131]. Three studies found only the gross tumor volume (GTV) dose to be predictive of acute Grade 2 GI toxicity [132][133][134]. A retrospective study showed a trend toward fewer late complications among the patients treated with a dose of <60 Gy: the late toxicity rate was 14% for a dose <60 Gy compared to 37% for a dose of !60 Gy (p ¼ .04) [36].…”

Association between dose-volume parameters and acute bone marrow suppression in rectal cancer patients treated with concurrent chemoradiotherapy

“…The study of Mell et al [ 6 ] has revealed that white blood cell nadir is correlated with female gender, low BMI and lymph node positivity, and neutrophil nadir is correlated with female gender and low BMI. Moreover, it has been reported that ≥ Grade 2 leukopenia is associated with cycle number of chemotherapy, and ≥ Grade 2 neutropenia is associated with cycle number of chemotherapy and T stage [ 18 ]. Single factor analysis in the present has demonstrated that acute bone marrow suppression is not significantly associated with gender, age, BMI and clinical stage of rectal cancer patients.…”

Robust dose planning objectives for mesorectal radiotherapy of early stage rectal cancer – A multicentre dose planning study

“…Bowel: For rectal cancer patients, preoperatively treated with 3D-CRT, the absolute bowel volume receiving !15 Gy (V 15Gy ) has consistently been found to correlate with acute GI toxicity [7][8][9][10][11]. Studies of rectal [12], anal [13][14][15][16][17], prostate [18][19][20] and gynaecological [21][22][23] cancer patients treated with IMRT or arc therapy have found correlations between acute GI toxicity and dose levels from approximately 25-45 Gy, delivered in 25-28 fractions. For late GI toxicity in rectal cancer, the data is very limited.…”