Carcinoma rectum-radiotherapy perspective

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Christian Medical College and Hospital , Ludhiana

Christian Medical College and Hospital , Ludhiana

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  • 1. By Dr Parneet Singh
  • 2. Epidemiology  Colorectal caner is the third most frequently diagnosed cancer in the US men and women.  108,070 new cases of colon cancer and 40,740 new cases of rectal cancer in the US in 2008. Combined mortality for colorectal cancer 49,960 in 2008.  Worldwide approx. 1 million new cases p.a. are diagnosed, with 529,000 deaths.  Incidence rate in India is quite low about 2 to 8 per 100,000  Median age- 7th decade but can occur any time in adulthood  Lifetime risk   1 in 10 for men 1 in 14 for women
  • 3. Incidence in Large Bowel • Cecum 14 % • Ascending colon 10 % • Transverse colon 12 % • Descending colon 7% • Sigmoid colon 25 % • Rectosigmoid junct 0.9 % • Rectum 23 %
  • 4. Clinical Anatomy  12-15 cm from anal verge.  Diameter  4 cm (upper part)  Dilated (lower part)  Posterior part of the lesser pelvis and in front of lower three pieces of sacrum and the coccyx  Begins at the rectosigmoid junction, at level of third sacral vertebra
  • 5. Clinical Anatomy .  Ends at the anorectal junction, 2-3 cm in front of and a little below the coccyx  Taenia of the sigmoid colon form a continuous outer longitudinal layer of smooth muscle  Fatty omental appendices are discontinued
  • 6. Rectum is divided into 3 portions  3 distinct intraluminal curves ( Valves of Houston) Lower rectum : 3 – 6 cm from the anal verge Mid rectum: 6 cm to 8 -10cm from anal verge  Upper rectum: 8 cm to 12 -15cm from anal verge
  • 7. Peritoneal Relations  Superior 1/3rd of the rectum  Covered by peritoneum on the anterior surfaces and lateral  Middle 1/3rd of the rectum  Covered by peritoneum on the anterior surface  Inferior 1/3rd of the rectum  Devoid of peritoneum  Close proximity to adjacent structure including boney pelvis.
  • 8. Arterial Supply  Superior rectal A – from IMA; supplies upper and middle rectum  Middle rectal A- from Internal iliac A. (supplies lower rectum)  Inferior rectal A- from Internal pudendal A.
  • 9. Venous Drainage Superior rectal V- upper & middle third rectum Middle rectal V- lower rectum and upper anal canal Inferior rectal vein- lower anal canal
  • 10. Nerve supply  Sympathetic: L1- L3, Hypogastric plexus  ParaSympathetic: S2-S4
  • 11. Lymphatic drainage  Upper and middle rectum  Pararectal lymph nodes, located directly on the muscle layer of the rectum  Inferior mesenteric lymph nodes, via the nodes along the superior rectal vessels  Lower rectum  Sacral group of lymph nodes or Internal iliac lymph nodes  NODAL GROUPS Perirectal Common iliac Internal iliac Paraortic
  • 12. Lymphatic Drainage
  • 13. Aetiology  Etiological agents  Environmental & dietary factors  Chemical carcinogenesis.  Associated risk factors  Male sex  Family history of colorectal cancer  Personal history of colorectal      cancer, ovary, endometrial, breast Excessive BMI Processed meat intake Excessive alcohol intake Low folate consumption Neoplastic polyps.  Hereditary Conditions (FAP, HNPCC)
  • 14. Symptoms  Asymptomatic  Blood PR(60%)  Change in bowel habit(43%) (diarrhoea, constipation,       narrow stool, incomplete evacuation, tenesmus) Occult bleeding(23%) Abdominal discomfort (20%)(pain, fullness, cramps, bloating, vomiting) Weight loss, tiredness Back Pain Urinary symptoms Pelvic pain(5%) indicating nerve trunk involvement
  • 15. Acute Presentations  Intestinal obstruction  Perforation  Massive bleeding
  • 16. Signs  Pallor  Abdominal mass  PR mass  Jaundice  Nodular liver  Ascites  Rectal metastasis travel along portal drainage to liver via superior rectal vein as well as systemic drainage to lung via middle inferior rectal veins.
  • 17. Signs  Signs of primary cancer  Abdominal tenderness and distension – large bowel obstruction  Intra-abdominal mass Digital rectal examination – most are in the lowest 12cm & reached by examining finger  Rigid sigmoidoscope  Signs of metastasis and complications  Signs of anaemia  Hepatomegaly (mets)  Monophonic wheeze  Bone pain
  • 18. WHO Classification of Rectal Carcinoma  Adenocarcinoma in situ / severe dysplasia  Adenocarcinoma  Mucinous (colloid) adenocarcinoma (>50% mucinous)  Signet ring cell carcinoma (>50% signet ring cells)  Squamous cell (epidermoid) carcinoma  Adenosquamous carcinoma  Small-cell (oat cell) carcinoma  Medullary carcinoma  Undifferentiated Carcinoma
  • 19. Dukes classification Dukes A: Invasion into but not through the bowel wall   Dukes B: Invasion through the bowel wall but not involving lymph nodes  Dukes C: Involvement of lymph nodes  Dukes D: Widespread metastases
  • 20. Modified astler coller classification Stage A : Limited to mucosa  Stage B1 : Extending into muscularis propria penetrating through it; nodes not involved but not  Stage B2 : Penetrating through muscularis propria; nodes not involved  Stage C1 : Extending into muscularis propria but not penetrating through it. Nodes involved  Stage C2 : Penetrating through muscularis propria. Nodes involved  Stage D: Distant metastatic spread
  • 21. TX T0 Tis T1 T2 TNM Classification Primary tumor cannot be assessed No evidence of primary tumor Carcinoma in situ: intraepithelial or invasion of lamina propria Tumor invades submucosa Tumor invades muscularis propria T3 Tumor invades through the muscularis propria into pericolorectal tissues T4a Tumor penetrates to the surface of the visceral peritoneum T4b Tumor directly invades or is adherent to other organs or structures Tis T1 T2 T3 T4 Mucosa Muscularis mucosae Submucosa Muscularis propria Subserosa Serosa Extension to an adjacent organ
  • 22. TNM Classification
  • 23. Stage grouping Stage 0 I IIA IIB T Tis T1 T2 T3 T4 N N0 N0 N0 N0 N0 M M0 M0 M0 M0 M0 Dukes A A B B MAC A B1 B2 B3 IIIA IIIB IIIC IV T1-2 T3-4 Any T Any T N1 N1 N2 Any N M0 M0 M0 M1 C C C - C1 C2/C3 C1/C2/C3 D
  • 24. Stage 0 Rectal Cancer  Known as ―cancer in situ,‖ meaning cancer is located in the mucosa.
  • 25. Stage I Rectal Cancer  The cancer has grown through the mucosa and invaded the muscularis (muscular coat)
  • 26. Stage II Rectal Cancer  The cancer has grown beyond the muscularis of the colon or rectum but has not spread to lymph nodes
  • 27. Stage III Rectal Cancer  Cancer has spread to the regional lymph nodes (lymph nodes near the colon and rectum)
  • 28. Stage IV Rectal Cancer  Cancer has spread outside of colon or rectum to other areas of the body
  • 29. Prognostic factors  Good prognostic factors  Old age  Gender(F>M)  Asymptomatic pts  Polypoidal lesions  Diploid  Poor prognostic factors          Obstruction Perforation Ulcerative lesion Adjacent structures involvement Positive margins LVSI Signet cell carcinoma High CEA Tethered and fixed cancer
  • 30. Stage and Prognosis Stage 5-year Survival (%) 0,1 Tis,T1;No;Mo > 90 I II T2;No;Mo T3-4;No;Mo 80-85 70-75 III T2;N1-3;Mo 70-75 III T3;N1-3;Mo 50-65 III IV T4;N1-2;Mo M1 25-45 <3
  • 31. Japanese Scientists train Dogs to detect Colorectal Cancer ( Gut, 2011)
  • 32. Diagnostic Workup  History—including family history of colorectal cancer or polyps  Physical examinations including DRE and complete pelvic examination in women: size, location, ulceration, mobile vs. tethered vs. fixed, distance from anal verge and sphincter functions.  Proctoscopy—including assessment of mobility, minimum diameter of the lumen, and distance from the anal verge  Biopsy of the primary tumor
  • 33. Diagnostic Evaluation  General Clinical features.  Lab. Studies Complete blood cell count Blood chemistry profile CEA  Evaluation  Determination of Occult Blood Digital Rectal Examination Proctosigmoidoscopy Flexible Fibreoptic Sigmoidoscopy & Colonoscopy. Barium Enema • Urologic Evaluation • Other Imaging studies • CT, USG, MRI, Chest X-ray, FDG- PET scan, Endorectal U/S.
  • 34. Colonoscopy or barium enema To evaluate remainder of large bowel to rule out synchronous tumor or presence of polyp syndrome. Figure: Carcinoma of the rectum. Doublecontrast barium enema shows a long segment of concentric luminal narrowing (arrows) along the rectum with minimal irregularity of the mucosal surface.
  • 35. Transrectal Ultrasound  Used for clinical staging.  80-95% accurate in tumor     staging 70-75% accurate in mesorectal lymph node staging Very good at demonstrating layers of rectal wall Use is limited to lesion < 14 cm from anus, not applicable for upper rectum, for stenosing tumor Very useful in determining extension of disease into anal canal (imp to plan sphincter preserving surgery) Figure.Endorectal ultrasound of a T3 tumor of the rectum, extension through the muscularis propria, and into perirectal fat.
  • 36. EUS : Accuracy EUS CT Depth of infiltration T staging 91% 71% N staging 87% 76%
  • 37. CT Scan  Part of routine workup of patients  Useful in identifying enlarged pelvic lymph-nodes and metastasis outside the pelvis than the extent or stage of primary tumor  Limited utility in small primary cancer  Sensitivity 50-80%  Specificity 30-80%
  • 38. CT Scan  Ability to detect pelvic and para-aortic lymph nodes is higher than peri-rectal lymph nodes(75% to 87% vs. 45%) Accuracy T stage 60-80% Accuracy N stage 60-75% Liver met. 70-79%
  • 39. Figure: Rectal cancer with uterine invasion. CT scan shows a large heterogeneous rectal mass (M) with compression and direct invasion into the posterior wall of the uterus (U). Figure: Mucinous adenocarcinoma of the rectum. CT scan shows a large heterogeneous mass (M) with areas of cystic components. Note marked luminal narrowing of the rectum (arrow).
  • 40. Magnetic Resonance Imaging (MRI)  Greater accuracy in defining extent of rectal cancer extension and also location & stage of tumor  Helpful in lateral extension of disease, critical in predicting circumferential margin for surgical excision.  Different approaches (body coils, endorectal MRI & phased array technique)
  • 41. Figure: Normal rectal and perirectal anatomy on high-resolution T2-weighted MRI. Rectal mucosa (M), submucosa (SM), and muscularis propria (PM) are well discriminated. Mesorectal fascia appears as a thin, low-signal-intensity structure (arrowheads) and fuses with the remnant of urogenital septum making Denonvilliers fascia (arrows). Figure: Mucinous adenocarcinoma of the rectum. T2-weighted MRI shows high signal intensity (arrowheads) of the cancer lesion in right anterolateral side of the rectal wall.
  • 42. PET with FDG  Shows promise as the most sensitive study for the detection of metastatic disease in the liver and elsewhere.  Sensitivity of 97% and specificity of 76% in evaluating for recurrent colorectal cancer. cancer rectum prostate Small bowel bladder pubic bone
  • 43. Aims of treatment  Local control  Long-term survival  Restoration of bowel continuity and Preservation of anal sphincter.  Bladder and sexual function and maintenance or improvement in QOL.  Careful preoperative screening is crucial in determination of the location of lesion and its depth of invasion
  • 44. Treatment Surgery Chemotherapy Radiotherapy
  • 45. Treatment Overview  Sx mainstay of treatment.  After curative resection the 5 year survival drops from 80% in stage I to about 40% in stage III disease.  Local recurrence remains a major site of failure ranging from 5% in few selected series to about 40% in most reports.  LF associated with devastating symptoms that severely affects the QOL & difficult to salvage
  • 46. Principles of surgical management  Removal of primary tumor with adequate margin.  T/t of draining LN.  Restoration of function  ―En bloc‖ resection if necessary
  • 47. PELVIC SUBSITES Five subsites :predominant areas at risk for local recurrence:  Mesorectal subsite (MS),  Posterior pelvic subsite (PPS)  Lateral pelvic subsite (LPS)  Inferior pelvic subsite (IPS)  Anterior pelvic subsite (APS)
  • 48. PATERN OF NODAL RECURRENCE  MS less common as it gets totally removed in TME  PPS most common site of nodal recurrence 22 to 49% in various series.  LPS around 21%  IPS around 3 to 11%  APS around 5 to17%
  • 49. Surgical procedures for Rectal ca  APR ( abdomino-perineal resection).  LAR ( Low ant. Resection) Radical  Proctectomy & colo-anal anastomosis  Local excision    Transanal excision Post. Proctotomy Non-Radical Trans-anal endoscopic microsurgery(TEM).  Ablative procedures Endoscopic surgery Fulguration
  • 50. Local excision  For superficially invasive (T1) tumors with low       likelihood of LN metastases Total biopsy, with further T/t based on pathology Tumors within 8 to 10 cm of anal verge, Encompass less than 40% of circumference of bowel wall, well or moderately well differentiated histology, No pathological evidence of venous or lymphatic vessel invasion on biopsy With unfavorable pathology patient should undergo total mesorectal excision with or without sphincterpreservation:  Positive margin (or <2 mm), lymphovascular invasion,  Poorly differentiated tumors, T2 lesion
  • 51. Local Excision Techniques  Transanal Excision.  Post proctotomy.  TEM  Fulguration  Endoscopic laser  Staging of such lesions should be performed using EUS to minimize likelihood of doing a local excision for T3 tumors.
  • 52. LAR  For tumors in upper/mid rectum allows preservation of anal sphincter  Join colon to low rectum  Permanent colostomy if tumor too low w  Reduced ability to define distant disease  Difficulty localizing lesion  OR time and costs
  • 53. Abdomino-perineal resection  For tumors of distal rectum(lower 1/3rd) with distal edge up to 6 cm from anal verge  Associated with permanent colostomy and high incidence of sexual and genitourinary dysfunction
  • 54. Procedure  Through combined abdominal and perineal incisions, the anus, rectum, and sigmoid colon are removed en bloc.  Also called Miles Resection  The proximal end of the bowel is exteriorized through a separate stab wound as a colostomy.  The distal end is pushed into the hollow of the sacrum and removed via perineum  Performed to treat cancer of the lower rectum—and diseases are too low for use of stapling devices
  • 55. Heavy purse string suture around anus to occlude it
  • 56. Colon and Rectum are delivered through the perineal resection
  • 57. Total mesorectal excision  Local failures are most often due to inadequate surgical clearance of radial margins.  Conventional resection violates the mesorectal circumference during blunt dissection, leaving residual mesorectum.  Excision of fascia enveloping the fat pad around the rectum  TME involves precise dissection and removal of the entire rectal mesentery as an intact unit.  Local recurrence with conventional surgery averages approx. 25-30% vs. TME 4-7% by several groups (although several series have higher recurrence)
  • 58. TOTAL MESORECTAL EXCISION
  • 59. Total Mesorectal Excision
  • 60. Pelvic Exenteration The surgeon removes the rectum as well as nearby organs such as the bladder, prostate, or uterus if the cancer has spread to these organs. A colostomy is needed after this operation. If the bladder is removed, a urostomy (opening to collect urine) is needed. High Anterior Resection 15 cm Low Anterior Resection Ultra-low Anterior Resection Abdominoperineal Resection (APR)
  • 61. Complications of Surgery  Bleeding  Infection  Anastomotic Leakage  Blood clots  Anesthetic Risks
  • 62. SUMMARY OF BOWEL FUNCTION IN THE 2 GROUPS Non-Radiation (59 Patients) No. of bowel movements/day Medican (range) 4 Clustering 5 Awoken at night for movement Incontinence None Occasional Frequent Wear a pad Perianal skin irritation Regularly use Lomotil ± Imodium Unable to differentiate stool from gas Liquid consistency (sometimes or always) Unable to defer defecation >15 min Need to defecate again within 30 min Bowel function different to preoperative 2 (1-7) 83% 3% 14% 14% – 93% 7% 0% 10% 12% 5% 15% 5% 19% 37% 61% Chemoradiotherapy (41 Patients) 7 (1-20) 22% 42% 37% 46% – 44% 39% 17% 41% 41% 58% 39% 29% 78% 88% 93% p Value <0.001 – – – <0.001 <0.001 – – – <0.001 <0.001 <0.001 0.009 0.001 <0.001 <0.001 0.001 JH012804
  • 63. Adjuvant therapy Chemotherapy Radiation therapy with or without chemotherapy
  • 64. Purpose of Radio(chemo)therapy  To lower local failure rates and improve survival in resectable cancers  To allow surgery in primarly inoperable cancers  To facilitate a sphincter-preserving procedure  To cure patients without surgery: very small cancer or very high surgical risk
  • 65. Chemotherapy agents       5Fu Leucovorin Oxaliplatin Irinotecan Bevacizumab cetuximab Combinations  FOLFOX  FOLFIRI  Leucovorin/5FU  Capecitabine  NIGRO  Bevacizumab in combination with the above regimens.
  • 66. PREOPERATIVE CHEMORADIATION  NSABP R-03 : improved DFS & OS  German trial : improved locoregional control.  REGIMENS :  5- FU : 225 mg/ m2 – daily continous infusion  Capecitabine : 825 mg/ m2 BD on days of radiation  5- FU : 400 mg / m2 IV bolus + leucovorin 20 mg /m2 IV bolus for 4 days : wk 1 & wk 5.
  • 67. POSTOPERATIVE CHEMORT :  EORTC 22921 trial : improved DFS & OS.  MOSAIC trial : Addition of oxaliplatin + 5- FU + leucovorin . REGIMENS :  5-FU : bolus weekly regimen ( leucovorin 20 mg/m2 over 2 hrs : 5- FU 500 mg/ m2 bolus  if no neoadjuvant chemoRT :  Weekly Roswell Park regimen : 5-FU + leucovorin ( leucovorin 500 mg /m2 given over 2 hrs followed by 5-FU bolus ) : weekly over 6 wks then 2 wks rest .  mFOLFOX 6  Capecitabine 1000 – 1250 mg/ m2 from day 1-14 ( 21 day cycle )
  • 68. Role of Radiotherapy  Neo-adjuvant/Adjuvant RT in resectable Ca Rectum pre-op post-op  RT in locally advanced rectal cancer pre-op for down staging IORT  Definitive RT unfit for surgery  Palliative RT – Pain, bleeding etc.
  • 69. ADVANTAGES OF PRE OP CT+RT • Down staging, hence increased resectability • Decreased risk of dissemination during surgery. • Radiation more effective with tumour cells highly vascular. • Less serious bowel toxicity due to easy exclusion. • Possibility of increasing sphincter preservation in borderline cases.
  • 70. TARGET VOLUME  Site of local involvement  spread to other organ - sacrum, vagina or prostate  Whole of the sacrum  Posterior margin should be beyond the sacrum  Anterior border 2-3 cm anterior to the promontry of sacrum to include common iliac LN
  • 71. Positioning  Prone position with belly board  Purpose is to displace bowel superior and anteriorly & bladder anteriorly  Bladder distension  Blocks are used to spare the posterior muscle and soft tissues behind the sacrum and small bowel.
  • 72. Treatment energy  PA portal with 6MV to decrease bladder dose  Lateral portal requires 10/15 MV to increase depth dose and decrease dose to hip joints  30 degree wedges improves distribution  Portals  4 fields (AP, PA, two lateral fields)  3 fields (PA, two lateral fields)  2 fields(AP,PA-rarely used)
  • 73. PA Borders – Pre Op Case In most cases upper border  lies at L5-S1 junction to cover Sacral promontary.  Inferior margin should be 34 cm below inferior tumour extent on sigmoidoscopy.  For upper rectal Ca, inferior border upto dentate line( cover all mesorectum)  Lateral border -1.5 cm beyond the bony pelvic wall
  • 74. Lateral portal  Upper Border- L5-S1  Lower Border 3-5 Cm below inferior Tx extension  Posterior border should be atleast 1 cm behind sacral convexity  Anterior border at pubic symphysis*(T3-T4)
  • 75. Issues in Postoperative RT of Rectum  Increased risk of bowel toxicity Adhesions Bowel sags in pelvic cavity Large portals 1. 2. Anastomotic site in ANTERIOR RESECTION Perineal scar in APR
  • 76. PA Borders – Post Op Case  In case of APR, inferior border should cover perineal scar  8-30% scar recurrence if scar not included in field  While only 2% reoccur if scar included in portal
  • 77. Lateral Borders – Post Op Case  In case of APR, inferior border should cover perineal scar
  • 78. Dose Distribution: 3 Fields / 30w
  • 79. Dose Distribution: 3 Fields / 45w
  • 80. DVH
  • 81. 3 Field / Open
  • 82. Bilateral Portals
  • 83. Portals- Two Fields : APPA  Parallel opposing not commonly used  High dose to bladder and bowel  Used in palliative cases & when bladder or anterior wall involved
  • 84. 2 Fields AP / PA
  • 85. DVH
  • 86. Pre-Op radiotherapy  Short course 25 Gy in 5 daily fractions of 5 Gy given in 1 week.  Long course  Phase 1 45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.  Phase 2 (optional) 5.4–9 Gy in 3–5 daily fractions of 1.8 Gy(2 lat. Fields)
  • 87. Post-Op Radiotherapy  Phase 1  45 Gy in 25 daily fractions of 1.8 Gy given in 5 week  Phase 2 (optional)  5.4–9 Gy in 3–5 daily fractions of 1.8 Gy(2 lat. fields)
  • 88. Palliative radiotherapy  Phase 1  45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.  Phase 2 (optional)  5.4–14.4 Gy in 3–8 daily fractions of 1.8 Gy(2 lat fields)  A hypofractionated regimen can be used  30–36 Gy in 5–6 fractions of 6 Gy once weekly given in 5– 6 weeks.
  • 89. Dose limitations  Small bowel- 45–50 Gy  Femoral head and neck- 42 Gy  Bladder -65 Gy  Rectum- 60 Gy
  • 90. CONTOURING GUIDELINES
  • 91. TARGET VOLUMES  CTVA: Defined to be the regions that would always be treated for rectal cancer  Internal iliac  Pre-sacral  Peri-rectal  CTVB:  External iliac nodal region  CTVC:  Inguinal nodal region
  • 92. GUIDELINES  Lower Pelvis: The caudal extent minimum of 2 cm caudal to gross disease, including coverage of the entire mesorectum to the pelvic floor Extension of CTVA does not need to go more than a few millimeters beyond the levator muscles unless there is radiographic evidence of extension into the ischiorectal fossa For very advanced anal or rectal cancers, extending through the mesorectum or the levators, add ~1-2 cm margin up to bone wherever the cancer extends beyond the usual compartments An MRI and/or PET/CT scan is strongly recommended in such cases.
  • 93. Mid pelvis The posterior and lateral margins of CTVA should extend to lateral pelvic sidewall musculature or, where absent, the bone. Anteriorly extend CTVA to ~1 cm into the posterior bladder, to account for day-to-day variation in bladder position. Include the posterior portion of the internal obturator vessels (which lie between the external and internal iliacs in the mid pelvis) with CTVA.
  • 94. Upper pelvis:  Superior extent - the rectosigmoid junction or 2 cm proximal to the superior extent of macroscopic disease in the rectum/peri-rectal nodes.  This defines how much of the distal large bowel within CTVA.  Properly cover the internal iliac and pre-sacral regions.  The most cephalad aspect of CTVA - the common iliac vessels bifurcate into external/internal iliacs (landmark: sacral promontory).
  • 95. Indications for elective irradiation (CTVB+CTVC) Elective coverage of the inguinal and external iliac regions should be routine for anal carcinoma. For rectal carcinomas extending into gynecologic or genitourinary structures, the external iliac region should be added (i.e. elective nodal coverage = CTVA + CTVB for these cases). Include the external iliacs for rectal cancers that extend into the anal canal. Electively irradiate the inguinal nodal region for rectal adenocarcinomas that extend to the anal verge or peri-anal
  • 96. OAR The femoral head and neck should be avoidance structures. The small and large bowel are important structures to consider when planning treatment. The entire abdominal contents need to be contoured up to ~ 1 cm above the PTV. Absolute volume of bowel (in cc) is more important than relative volume (in %).
  • 97. IORT radiation therapy (IORT) delivers a  Intra-operative concentrated dose of radiation therapy to a tumor bed during surgery  Dose range from 1250-2000cGy.  Patient must be a surgical candidate in order to be eligible for IORT  Reserved for pts. with early-stage disease.
  • 98.  Maximum effect, while minimizing recurrence  Delivered immediately after tumor is removed, helping to destroy the microscopic tumor cells that may be left behind  The tumor site is typically at high risk for recurrence & traditional RT requires a recovery period after surgery, which leaves microscopic disease in the body for longer  Spares healthy tissues and organs  Shortened treatment times  IORT T/t itself takes about 4 to 5 min.
  • 99.  A "boost" for traditional radiation pts.  Patients who must receive additional radiation therapy following surgery can receive a boost of radiation during IORT After they have recovered from the surgical procedure, they can continue with their RT with fewer complications.
  • 100. Endocavitary Radiation  Propagated initially by Papillon and Sischy  High doses low energy radiation delivered using 50 KVp unit  Initially utilised applicator cones of 2.4 – 2.9 cm dia  Later intra-luminal catheters were used after development of after-loading techniques.  Dose at 1 cm depth = 1/3 rd of surface dose  Since, very small volume very high doses can be tolerated  Multiple treatment done till CR achieved
  • 101. Treatment Recommendations Stage Rectal cancer ~5-year LF/OS I • TME with APR or LAR. • If pT1-2N0, no adj. treatment. • Local excision for favorable tumors (<3 cm size, <30% circumference, within 8 cm of anal verge, well-moderately differentiated; margin >3 mm, no LVSI/PNI).  favorable T1 lesions- observation.  T2 lesions - adjuvant 5-FU/RT <5% LF 90% OS II and III (locally resectabl e) • Pre-op 5-FU/RT LAR/APR adjuvant 5FU-based therapy × 3 cycles (preferred) • If surgery initially  then adjuvant 5-FU × 2 cycles  concurrent chemoRT  5-FU ×2 cycles T3N0 and T1-2N1: 5–10% LF 80% OS T4N0 and T3N1: 10–15% LF 60% OS T4N1 and T3/4N2: 15–20% LF 40% OS
  • 102. Stage III (T4/ Locally unresectable ) Rectal cancer If obstructed, diverting colostomy or stent placed  definitive treatment. 5-FU/RT  resection if possible. Consider IORT for microscopic disease (after 50 Gy EBRT, give IORT 12.5–15 Gy) or brachytherapy for macroscopic disease  adjuvant 5-FU-based therapy* IV Individualized options, including combination 5-FU-based chemo alone, or chemo ± resection ± RT Recurrent Individualized options. If no prior RT, then chemoRT  surgery ± IORT or brachytherapy. If prior RT, then chemo surgery ± IORT or brachytherapy as appropriate. ~5-year LF/OS
  • 103. Clinical Trials
  • 104. Pre-op RT vs. surgery alone Swedish Rectal Cancer Trial(NEJM 1997;336:980 ): 1168 patients randomised to 25 Gy (5x5) PRT or no RT. Surgery alone Preop. RT Rate of local recurrence 27% 11% p<0.001 5-year overall survival 48% 58% p=0.004 Dutch Colorectal Cancer Group (Kapiteijn E. NEJM 2001;345:638): 1861 patients randomised TME vs PRT+TME TME PRT+TME Recurrence rate 2.4% 8.2% OS ns ns
  • 105. Pre-op vs. post-op Chemo RT Randomized trial of the German Rectal Cancer study Group (Sauer R et al. N Engl J Med 2004;351:1731-40):  cT3 or cT4 or node-positive rectal cancer  50.4 Gy (1.8 Gy per day)  5-FU: 1000 mg/m2 per day (d1-5) during 1. and 5. week Preop CRT Patients 5 y. OS 5 y. local relapse G3,4 toxic effects Postop CRT N=415 76% 6% 27% N=384 74% p=0.8 13% p=0.006 40% p=0.001 • Increase in sphincter-preserving surgery with preop Th.
  • 106. • MRC CR07/NCIC-CTG C016 (Sebag-Montefiore et al. 2009): 1350 pt. with resectable rectal cancer randomized. ▫ 25 Gy/5# + Surgery (TME) ▫ Surgery (TME) + (45 Gy & 5 FU) CRT 5 y. OS 5 y. local relapse DFS Preop RT 80.8% 4.4% 79.5% Postop 78.7% 10.6% 74.5%
  • 107. Polish Trial • Polish Study (Br J Surg. 2006): 316 pts with resectable T3- 4 rectal cancer, no sphincter involvement, tumor palpable on DRE (1999-2002). – RT  short-course RT with 5 Gy/d x 5 days + Surgery (TME) – CRT  50.4 Gy (1.8 Gy /# over 5.5 weeks) + bolus 5-FU 325 mg/m²/d + LV x 5 days 1st and 5th wks of RT + Surgery (TME) Preop SCRT Preop LCRT 5 y. OS 5 y. local relapse DFS 67.2% 9.0% 58.4% 66.2% 14.2% 55.6%
  • 108. Post-op chemo, RT, and/or ChemoRT  GITSG 7175 (Thomas and Lindblad, 1988): 227 patients with stage B2-C rectal CA randomized postoperatively to:  no adjuvant therapy vs.  chemo alone vs.  RT alone vs.  concurrent chemoRT. Result: Chemo-RT arm improved 5-year OS (54%) and LR(10%) over observational arm OS (27%) & LR (25%).  Mayo NCCTG 79-47-51 (NEJM 1991): 204 patients with T3/4 or LN+(B2-C) randomized to  post-op RT (45–50.4 Gy) vs.  chemoRT (bolus 5-FU concurrent). Result: Chemo-RT improved LF (25 14%), DFS, and OS (48 58%) vs. RT alone.
  • 109. Thank You !!