Esophageal cancer-role of RT


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  • Oblique portals for the primary and ant portal for nodesFour filed box technique (compensator to be used)Anterior wedge pair fieldsIMRTCT planning: IV contrast for mediastinal, abdominal and coeliac vessels
  • Change photoHow anterior field marked on post side
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  • 5-FU, 5-fluorouracil; ECOG, Eastern Cooperative Oncology Group; GEJ, gastroesophageal junction; OS, overall survival; PD, progressive disease; PS, performance score; R, randomization. Data from the phase III ToGA trial clearly put trastuzumab on the map for patients with HER2-overexpressing gastric and GE junction cancer. To accrue a sufficient number of patients with HER2-positive gastric cancers, 3800 patients were screened for HER2 expression, and eventually 22% of these patients (n = 810) were found to be HER2 positive according to the study protocol. Of the 810 patients who were considered eligible for the study, 584 were ultimately randomized to receive either 5-fluorouracil or capecitabine plus cisplatin with or without trastuzumab. The dose of capecitabine used was 1000 mg/m2 twice daily, about the standard dose, administered for 2 weeks on and 1 week off. Most investigators used capecitabine and not the infusional 5-fluorouracil variation. The primary endpoint of this trial was overall survival.
  • Rtog 8501: acute Gr3=25%, gr4= 3% longterm 23%, 2%. INt0123: 43%, 26%. 24%, 13%.
  • Esophageal cancer-role of RT

    1. 1. Management of carcinoma esophagus DR BHARTI DEVNANI MODERATOR:- DR ANJALI K. PAHUJA
    2. 2. Localised disease Metastasis Definitive therapy Palliative therapy Diagnostic workup . At the time of diagnosis, approximately 80% patients have locally advanced or distant disease
    3. 3. EVOLUTION OF TREATMENT Non surgical treatment  Radiation therapy alone  Combined modality therapy(CT+RT)  Intensification of the radiation dose Surgical treatment Sx alone Sx+adjuvant Preop CT + Sx
    4. 4. RT ALONE
    5. 5. 6 RADIATION ALONE AUTHOR NO OF PTS DOSE 2 YRS SURVIVAL 5 YRS SURVIVAL Pearson 208 50Gy/4Wks NA 17% Beatty et al 344 >40Gy to > 50Gy 21% 0% Schuchman n et al 127 <45Gy >45 Gy 0% 0% Newaishy et al 444 50-55Gy/4 Wks 19% 9% Okawa et al 96 NR 9%(I-20%,II- 10%,III-3%,IV- 0%) Lederman et al 263 11%(yrs) 7%
    7. 7. RTOG 85-01 TRIAL(RT ALONE V/S CMT) R A N D O M I S E Wk 1 50Gy/25 fractions Wk 5 Wk 11 CDDP 75mg/m2 Day 1 and 5-FU 1gm/m2 C.I. day 1- 4 CT+RT RT Wk 8 64Gy/32 fractions
    8. 8. RESULTS OF RTOG 85-01 TRIAL Comp- liance Gr III toxicity Gr IV Gr V Local failure Dist failure Median and 5yr survival CT+RT (n=61) 54% 44% 20% 3% 43% 22% 12.5 mo, 27% RT (n=60) 83% 25% 3% 0 64% 38% 8.9 mo, 0% P-value Sig Sig Sig Sig Sig Sig p<0.0001 All patients who received RT alone were dead of disease by 3 years. Established chemoradiation as the conventional nonsurgical treatment for esophageal cancer Herskovic A et al. NEJM 1992;326:1593-1598
    9. 9. 10 CONCURRENT CT+RT- META ANALYSIS OF 11RCT Cochrane Database of Systematic Reviews
    10. 10. RESULTS OF METANALYSIS  Concomitant RTCT provided significant reduction in mortality with a HR of 0.73.  The absolute survival benefit for RTCT at 1yr and 2 yr was 9%and 4% respectively.  There was an absolute reduction of local recurrence rate of 12%
    12. 12.  The cumulative incidence of fistula was 18%/year and the crude incidence was 14%.  Esophageal fistulas were treatment-related rather than tumor-related of the six treatment-related fistulas, three were fatal .  Occurred in the region of the brachytherapy.  Five of the six patients developing fistulas received 15 Gy brachytherapy dose. (median-3.9 months)  The other patient received just one fraction of 5 Gy and developed a fistula within 0.5 months.
    14. 14. 17 R A N D O M I S E Wk 1 50.4Gy/28 fractions Wk 5 Wk 13 CDDP 75mg/m2 Day 1 and 5-FU 1gm/m2 C.I. day 1- 4 Standard CT+RT CT + High dose RT Wk 9 64.8Gy/36 fractions Wk 1 Wk 5 Wk 11 Wk 15 Minsky BD et al. JCO 2002;20:1167-1174
    15. 15. No significant difference in survival(p=NS) MS-18 v/s 13 months 2 yr survival—40% v/s 31% No significant difference in time to first failure(52% v/s 56%) (local /regional failure or locoregional persistance of cancer) This trial demonstrated that for patients who receive concurrent chemotherapy with radiation, higher doses of radiation therapy do not offer a local/regional control or survival advantage.
    17. 17. 20 PRE OP.CT+RT+S VS S AUTHOR MEDI AN FOLL OW UP REGIMEN NO OF PTS Ro resection/ Dist Met PATH CR LOCOREG FAILURE 3-Yr Surviv al SURVIVAL DIFF Urba et al 8.2 5fu+cddp+Vbl+R T+S S 50 50 90 60% 90 65% 28 - 19% 42% P=0.02 30 16 p=0.15 Boset et al 4.6 Cddp+RT+S S 143 138 81 69 26 --- 34 36 NS Walsh et al 1.5 5fu+cddp+RT+S S 58 58 NR NR 25 32 6 P+0.01 Burmeiste r et al 5.4 5fu+cddp+RT+S S 128 128 80 59 16 --- 35 30 NS Tepper et al 6.0 5fu+cddp+RT+S S 30 26 NR NR 33 13 15 39 16 P=0.008
    18. 18.  9 RCT  1116 patients
    19. 19. Three-year survival (odds ratio 0.66, 95% confidence interval 0.47 to 0.92; P 0.016). Rate of complete resection (odds ratio 0.53, 95% confidence interval 0.33 to 0.84; P 0.007).
    20. 20. Compared with surgery alone, neoadjuvant chemoradiation and surgery  Improved 3-year survival  Reduced local-regional cancer recurrence.  Higher rate of complete (R0) resection.  Pathological complete response in 21% patients  Survival benefit was most pronounced when CT+RT were given concurrently instead of sequentially
    21. 21. Lancet Oncol 2011; 12: 681–92
    22. 22. Provides strong evidence for a survival benefit of neoadjuvant chemoradiotherapy or chemotherapy over surgery alone in patients with oesophageal carcinoma. clear advantage of neoadjuvant chemoradiotherapy over neoadjuvant chemotherapy has not been established.
    24. 24. 46 Gy 20 Gy
    25. 25.  In patients with locally advanced thoracic esophageal cancers, especially epidermoid, who respond to chemoradiation, there is no benefit for the addition of surgery after chemoradiation compared with the continuation of additional chemoradiation.  chemoradiation alone entailed fewer early deaths and a shorter hospital stay  More locoregional relapses.  Because clinical prognostic factors donot help in choosing between both strategies, further studies comparing surgery and chemoradiation should search for newpredictive factors and evaluate new tools to detect early responders.  PET scan was reported to discriminate responders from nonresponders as early as 14 days after starting chemoradiation and should be re-evaluated in future studies.
    26. 26. The study suggests that there is no difference in clinical toxicity profiles or survival outcomes with either definitive chemoradiotherapy or chemoradiation followed by surgery in management of locally advanced esophageal cancer.
    27. 27.  Future studies are necessary to investigate dose escalation of chemoradiotherapy, thereby reducing the risk of treatment failures in patients treated without surgery.
    28. 28. RADIATION
    29. 29. The design and delivery of radiation therapy for esophageal cancer requires a knowledge of the –  Natural history of the disease  Patterns of failure  Anatomy,  Radiobiologic principles.  Use of proper equipment  Implementation of methods to decrease treatment- related toxicity  Close collaboration with the physics and technology staff are essential.  As radiation oncology is both an art and a science.
    30. 30. RADIOTHERAPY Curative Dose-50.4 Gy/28#  Conventional  Conformal  3 D CRT  IMRT  IGRT  Arc  Respiratory gating  Proton Palliative EBRT Dose-30 Gy/10# Brachytherapy 12 Gy/# 18 Gy/3#
    31. 31. TECHNIQUES OF RADIATION THERAPY  External beam radiotherapy  Important considerations for RT  Nearby vital structures: spinal cord. lungs, heart  Movement in target tissue and vital structures: lungs, heart  Variable density of tissues: lungs
    33. 33. SIMULATION  Extent of the disease should be known based on imaging  Barium swallow,  CT,  PET  Endoscopy.  During simulation, the patient is positioned, straightened, and immobilized on the simulation table.  Arms are generally placed overhead.  Palpable neck disease should be marked with a radio- opaque wire  Administration of oral contrast to delineate the esophagus is used.  Some authors recommend placing the patient in the prone position for treatment to displace the esophagus away from the spinal cord
    34. 34. Conventional technique TREATMENT PORTALS Parallel opposed AP-PA fields EBRT TECHNIQUES Initial phase (39.6-41.4 Gy) - 5cm prox and distal margins - 2 cm lateral margins
    35. 35. Off cord Boost: After 40-44Gy 3 field technique -- one direct anterior and two lateral/ posterior oblique Advantages - Homogeneous dose distribution - Tumor better covered - Critical organs are out of the field
    36. 36. ‘T’ shaped AP-PA field: Upper cervical esophagus lesion - Treated from laryngopharynx to carina - Supraclavicular and upper mediastinal LN s irradiated electively AP-PA fields with lung shielding BORDERS: Superior: Thyroid notch Lateral : Junction of medial 2/3rd and lateral 1/3rd clavicle Lower: Adequate margins from lesion (include upper mediastinal LNs) Shielding: 5 HVL lead shield from 1cm below the Clavicles Lung correction factor -Co60 - dose decreased by 4%/cm - For 4 MV - 3% /cm - 10 MV -2 %/cm of lung
    37. 37. NORMAL TISSUE TOLERANCE Organ TD5/5 Gy TD50/5 Gy Field size Spinal cord 47 50 - 70 20cm 5-10cm Heart 40 60 50 70 Whole 1/3rd Lung 17.5 45 24.5 65 Whole 1/3rd
    39. 39. •In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume. •Local failure and distant metastases remained the predominant problems. •A longitudinal margin of 3 cm from the GTV to the CTV1 is probably enough
    40. 40. BASIS OF OMITTING ENI Recurrence was with in GTV
    41. 41. 1. Recurrene pattern(in-field) Predominant failure pattern in with esophageal SCC was local in-field or distant failures. Regional nodal recurrence (out-of- field) was infrequent (8%) in the absence of elective node irradiation. 2. Biological behavior of the disease Esophageal cancer is characterized by a high rate of nodal involvement and its spread pattern is not always predictable. Also, skip node metastases are frequently observed. Thus the biological behavior of this disease makes it difficult to define in advance the extent of coverage of elective nodal irradiation. 3. Toxicities If distant lymph node areas were irradiated prophylactically, patients would then experience more severe radiation complications and have a poorer treatment tolerance.
    42. 42. In CRT for esophageal SqCC, ENI was effective for preventing regional nodal failure. TheUPPER THORACIC esophageal carcinomas had significantly more local recurrences than the middle or lower thoracic sites.
    43. 43. No global consensus on whether or not ENI should be performed.
    48. 48. TRASTUZUMAB + CHEMOTHERAPY IN ADVANCED HER2+ GASTRIC CANCER: TOGA STUDY  Rationale: a subpopulation of gastric cancers overexpress HER2 * (n = 584) R Patients with advanced gastric adenocancer screened for HER2 status (N = 3803) Stratified by ECOG PS, advanced vs metastatic, gastric vs GEJ, measurable disease, capecitabine vs 5-FU Patients with HER2+ advanced gastric cancer (n = 810; 22% of successful screenings) 5-FU or Capecitabine* + Cisplatin 80 mg/m2 q3w x 6 + Trastuzumab 6 mg/kg q3w until PD (8 mg/kg loading dose) (n = 294) 5-FU or Capecitabine* + Cisplatin 80 mg/m2 q3w x 6 (n = 290) Bang YJ, et al. Lancet. 2010;376:687-697.
    49. 49. Outcome Chemotherap y + Trastuzumab (n = 294) Chemotherap y Alone (n = 290) HR (95% CI) P Value Median OS, mos 13.8 11.1 0.74 (0.60- 0.91) .0046 Median PFS, mos 6.7 5.5 0.71 (0.59- 0.85) .0002 Established transtuzumab and chemotherapy is a new standard of care for Her-2 neu expressing advanced gastric and EGJ adenocarcinoma. Significant OS benefit Safety profile were similar
    51. 51. IMPORTANCE OF PALLIATIVE CARE IN CA ESOPHAGUS Majority of the patients diagnosed with advanced disease(80%) therefore palliation is an important goal.
    52. 52. 1.Dysphagia 2.Obstruction EBRT BT EBRT+CCT Surgery Endoscopic lumen restoration Stenting 3.Pain(WHO pain ladder) 4. Nausea and vomitting (Antiemetics) 5.Bleeding Acute bleeding Chronic bleeding 6.Tracheo-oesophageal fistula
    53. 53. Fractionated BT is the best modality of palliation in comparison to all other modalities.for advanced esophageal cancers. It offers best palliation both in terms of survival(6.2) as well as symptom free duration 40% pts were free of dysphagia for one yr. 16Gy/2# or 18 Gy/3#
    54. 54. Versus
    55. 55.  Dysphagia improved more rapidly after stent placement than after brachytherapy, but longterm relief of dysphagia was better after brachytherapy.  Stent placement had more complications than brachytherapy which was mainly due to an increased incidence of late haemorrhage .  No difference for median survival (p=0·23).  Quality-of-life scores were in favour of brachytherapy compared with stent placement.  Total medical costs were also much the same for stent placement (€8215) and brachytherapy (€8135). Due to better long-term relief of dysphagia with fewer complications brachytherapy is recommended as the primary treatment for palliation of dysphagia from oesophageal cancer.
    56. 56. BRACHYTHERAPY Procedure • After placing the patient in left lateral position, a fibre-optic endoscope is passed. • The esophagus will be evaluated for extent of residual tumor, presence of ulcer and stricture. • If suitable for brachytherapy, a stainless steel guide wire will be passed through the biopsy channel of the endoscope and passed beyond the tumor site • Depending upon the site of lesion, the length of selectron boogie will be adjusted by altering position of the mouth piece, so that lower end of the boogie is 2cm beyond the lower limit of initial lesion. • The boogie will be threaded over the guide wire, which is then withdrawn
    57. 57. BRACHYTHERAPY Prescription 1 cm from the mid-source / mid-dwell position without optimization
    59. 59. SURGICAL APPROCHES FOR ESOPHAGOGASTRECTOMY  Transthoracic approach  Transhiatal approch
    60. 60. TRANSTHORACIC APPROACH Right thoracotomy & laparotomy  Ivor lewis  Mckeown (with cervical anastomosis)
    63. 63. •Transient myelosuppression (30%) • Esophagitis • Dysphagia • Pneumonitis • Perforation with fistula or hemorrhage • Skin changes: hair loss, redness • Pericarditis • Nausea/ vomiting • LOW/LOA • Stenosis/ stricture Occurs in 60 % of cases Stricture requiring dilatation-15- 20 % • Pneumonitis/ pulmonary fibrosis • Esophagotracheobronchial fistulae • Aortic rupture and hemorrhage • Pericarditis with pericardial constriction • Transverse myeiltis • Myocardial damage • Radionecrosis of bone COMPLICATIONS OF CRT
    64. 64. PROBLEMS WITH TRIMODALITY  Haematological toxicity – 30 %  Mucositis Gr 3,4  Oesophagitis  Pulm complications (ARDS) 14 %  Surgical complications -  anastomotic leak 6 %  Local recurrence 6 %  Operative deaths 6 % TOXICITY TUMOUR CONTROL
    65. 65. MANAGING COMPLICATIONS  Smoking cessation  Nutrition maintenance: - Assess radiation tolerability before starting radiation - Plenty of fluids, frequent sips of cool liquids - Disprin and local anesthetic gargles - Avoid hot spicy, dry food - Ryles tube insertion: Grade 3-4 dysphagia/ <1500kcal/day  Respiratory physiotherapy: to improve pulmonary function  During radiation, check patient status at least once a week  Antiemetics, Antacids, soothening agents be prescribed when needed Treatment interruptions or dose reductions for manageable acute toxicities should be avoided.
    66. 66. THANK U
    67. 67. PHOTODYNAMIC THERAPY PRINCIPLE: - Uses photosensitiser (Hematoporphyrin) and red (WL=630nm) LASER - Resultant free radicals destroy DNA of rapidly dividing cells. INDICATIONS:  Barrets esophagus  Early esophageal cancer  Persistant or recurrent esophageal cancer post RT, CCT, Sx ADVERSE EFFECTS: Local swelling and inflammation Photosensitivity: shield skin and eyes for 4 hours
    68. 68. SURGERY
    69. 69. Resection should include Lower esophagus to a point above azygos vein Celiac lymph nodes Left gastric lymph nodes Division of left gastric artery Proximal part of stomach Pyloroplasty