Radiation Oncology/Toxicity/Esophagus

Radiation Toxocity: Esophagus Etiology Dysphagia = disordered eating potentially caused by a number of mechanisms, both neurologic and non-neurologic Odynophagia = painful swallowing Swallowing process includes three phases coordinated from the brainstem Oral phase: bolus processing, propelling food from oral cavity to oropharynx. Voluntary process. Pharyngeal phase: propelling food from oropharynx downward. Closure of nasopharynx via soft palate, closure of airway via epiglottis, opening of upper esophageal sphincter. Involuntary process. Aspiration significant concern Esophageal phase: peristaltic movement to propel food into stomach. Lower esophageal sphincter opened Dysphagia may be caused by extrinsic compression of the esophagus, intrinsic narrowing of the esophagus, or disorders of the esophageal motility Extrinsic compression: Cervical LND, gastric cancer Intrinsic narrowing: Esophageal tumor, esophageal stricture Dismotility: achalasia, esophageal spasm, scleroderma Odynophagia suggests disruption of esophageal mucosa (inflammation) or muscle spasms Infection, particularly candida and HSV Pill esophagitis Reflux esophagitis Radiation esophagitis Ulcerated neoplasm Caustic agent (acid/alkali) ingestion Infectious esophagitis Bacteria rarely cause primary esophageal infection Most common forms (frequently seen with concurrent chemotherapy: Candida, HSV Immunosuppression-associated forms: CMV, HIV Treatment: Oral nystatin Ketoconazole or fluconazole for more extensive involvement or if immunocompromized Amphotericin B if evidence of systemic spread Radiation esophagitis Acute reaction leads to inflammation, dysphagia and/or odynophagia, and dysmotility Secondarily, patients can develop dehydration and weight loss Rarely, patients may develop obstruction, perforation, or fistulas Late toxicity usually involves fibrosis leading to stenosis Treatment is typically symptomatic Toxicity Scales NCI CTCAE v3.0 Adverse Event Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Dysphagia Symptomatic, able to eat regular diet Symptomatic, altered eating/swallowing; IV fluids <24 hrs Symptomatic, inadequate oral caloric/fluid intake, need IV fluids >24 hrs, TPN Life-threatening (obstruction, perforation) Death Esophagitis Asymptomatic findings Symptomatic, altered eating/swallowing; IV fluids <24 hrs Symptomatic, inadequate oral caloric/fluid intake, need IV fluids >24 hrs, TPN Life-threatening (obstruction, perforation) Death Fistula Asymptomatic Symptomatic, altered eating/swallowing; IV fluids <24 hrs Symptomatic, severe alteration, IV fluids >24 hrs, tube feeding, TPN Life-threatening Death Heartburn Mild Moderate Severe -- -- Perforation Asymptomatic Medical intervention; IV fluids <24 hrs Surgery required; IV fluids >24 hrs, TPN Life-threatening Death Stricture Asymptomatic Symptomatic, altered eating/swallowing; IV fluids <24 hrs Surgery required; IV fluids >24 hrs, TPN Life-threatening, require complete organ resection Death Ulceration Asymptomatic Symptomatic, altered eating/swallowing; IV fluids <24 hrs Surgery required; IV fluids >24 hrs, TPN Life-threatening Death RTOG Acute Morbidity Scoring Criteria Organ Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 EsophagusMild dysphagia or odynophagia, Topical anesthetics or NSAIDs,Soft diet Moderate dysphagia or odynophagia,Narcotic analgesics, Puree or liquid diet Severe dysphagia or odynophagia,Dehydration or weigh loss >15%, IV fluids, NGT, TPN Complete obstruction, ulceration, perforation, fistula Death RTOG/EORTC Late Morbidity Scoring Schema Organ Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Esophagus Mild fibrosis, Slight difficulty swallowing solids,No pain on swallowing Unable to take solid food normally,Swallowing semi-solid food,Dilatation may be indicated Severe fibrosis,Able to swallow only liquids, May have pain on swallowing,Dilation requiredNecrosis,Perforation,Fistual Death Emami Data   TD 5/5 TD 50/5 % Organ 3/3 2/3 1/3 3/3 2/3 1/3 Esophagus(stricture,perforation) 5500 5800 6000 6800 7000 7200 Comment in text: information leading to these estimates was less than adequate Acute vs. late toxicity was not specified Acute Incidence overall: 5-13%. Incidence with chemo/RT: 18-46%. RT with concurrent chemotherapy: MDACC, 2006 (2000-2003) - PMID 16839700 — "Risk factors for acute esophagitis in non-small-cell lung cancer patients treated with concurrent chemotherapy and three-dimensional conformal radiotherapy." Wei X et al. Int J Radiat Oncol Biol Phys. 2006 Sep 1;66(1):100-7. Retrospective. 215 pts treated with concurrent chemo/RT (127 also with induction CT) and 3D-CRT. Most used carbo/taxol. Median dose 63.5 Gy in 35 fractions. RT was AP/PA followed by oblique off-cord fields. 7% - Grade 0, 27% - Grade 1, 45% - Grade 2, 20% - Grade 3, 0.4% - Grade 4. Predictors for grade 3 or worse acute toxicity: On univariate - mean dose to esophagus, aV15 (absolute volume > 15 Gy, in mL) through aV45, rV10 (relative volume > 10 Gy, in %) through rV45. Only rV20 was found to be significant on multivariate analysis. Conclusion: keep rV20 < 45% and mean esophageal dose < 28 Gy to keep risk of grade 3 or higher esophagitis < 15%. Werner-Wasik RedJ 2000 - PMID 11020565 Werner-Wasik 1999 - PMID 10760427 Maguire PD Red J 1999 - PMID 10477012 PMID 15890421 - Belderbos J V35 PMID 15001251 - Bradley J A55, V60 PMID 15849822 - Qiao WB Dmax 60 PMID 12527046 - Singh AK Dmax > 58 Michigan, 2005 PMID 16256230 -- "Normal tissue complication probability modeling for acute esophagitis in patients treated with conformal radiation therapy for non-small cell lung cancer." (Chapet O, Radiother Oncol. 2005 Nov;77(2):176-81.) Retrospective. 101 inoperable NSCLC. Outcome: Grade 2+ esophagitis Toxicity: 16% G2-3, 0% G4-5. LKB model: TD50 = 51 Gy (1STD = 40-63 Gy), n = 0.44, m = 0.32 (suggests wider dose dispersion around 51 Gy). Volumetric thresholds (Grade 2-3): V40 = 36.6 Gy, V50 = 31.0 Gy, V60 = 23.7 Gy, Max dose = 73.6 Gy Takeda et al (Japan), 2005 - PMID 15936536 — "Dosimetric correlations of acute esophagitis in lung cancer patients treated with radiotherapy." Int J Radiat Oncol Biol Phys. 2005 Jul 1;62(3):626-9. 35 pts, NSCLC + SCLC. Daily fractions of 1.8-2 Gy. Most received concurrent chemo. Grade 1 & 2 acute esophagitis: V35 (mean was 28%) Langer et al, 1997 Grade 2 or worse: Esophageal length > 16 cm Bradley et al, 2004 Grade 2 or worse: surface area > 55 Gy; V60 Patel et al, 2004 1.2 Gy BID Grade 2 or worse: V50 Werner-Wasik, 2000 Grade 3 or worse: hyperfractionated worse than once daily Singh, 2003 Grade 3 or worse: max dose > 58 Gy PMID 15936540 -- "Anatomically-correct" dosimetric parameters may be better predictors for esophageal toxicity than are traditional CT-based metrics." (Kahn D, Int J Radiat Oncol Biol Phys. 2005) Conclusion: "The inclusion of corrections, based on anatomic realities, to DVH-based dosimetric parameters may provide dosimetric parameters that are better correlated with clinical outcomes than are traditional DVH-based metrics." In reirradiation: PMID 15936541 -- "Combination of longitudinal and circumferential three-dimensional esophageal dose distribution predicts acute esophagitis in hypofractionated reirradiation of patients with non-small-cell lung cancer treated in stereotactic body frame." (Poltinnikov IM, Int J Radiat Oncol Biol Phys. 2005) Median RT dose was 32 Gy with a median fraction size of 4 Gy Conclusion: "Reirradiation using hypofractionated three-dimensional radiotherapy and SBF immobilization is an effective strategy for palliation of symptoms in selected patients with recurrent NSCLC. The length of the esophagus in the RT field does not predict for AE. However, an increasing number of EDs displaying the combination of longitudinal and circumferential three-dimensional dose distribution along the esophagus is a valuable predictor for AE." Management Please see the Esophagitis Supportive Care page for further information