1. Speciality surgeon oncologist radiotherapist

Transcription

1 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN RANDOMISATION FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F1 (Page 1 of 3), version. 1/8/ GENERAL INFORMATION 1. Physician 1. Speciality surgeon oncologist radiapist. Surgery and Chemapy Center 3. Radiation Center. INCLUSION CRITERIA: Main questions must be Yes! 1. Biopsyproven, newly diagsed primary rectal adecarcima, i.e. with the lowest part of the tumour less than 16 cm from the anal verge using a rigid rectoscope or flexible endoscope Yes No. Locally advanced tumour fulfilling at least one of the following criteria on pelvic MRI indicating high risk of failing locally and/or systemically. Fill out all criteria! At least one should be yes: a. Clinical stage (c) T4a, i.e. overgrowth to an adjacent organ or structure like the prostate, urinary bladder, uterus, sacrum, pelvic floor or sidewall (according to TNM version 5, in version 7 this is T4b) b. ct4b, i.e. peritoneal involvement (TNM5, in version 7 this is T4a) c. Extramural vascular invasion (EMVI+) d. N, i.e. four or more lymph des in the mesorectum showing morphological signs on MRI indicating metastatic disease. Four or more des, whether enlarged or t, with a rounded, homogeneous appearance is thus t sufficient e. Positive MRF, i.e. within one mm from the mesorectal fascia f. Metastatic lateral des (lat LN+) 3. Staging done within 5 weeks before randomisation 4. Age 18 years 5. ECOG performance score 1 6. No evidence of metastatic disease as determined by CT scan of chest and abdomen or investigations such as PET scan or biopsy if required 7. Adequate bone marrow function with platelets 1 x 1 9 /l; WBC 4 x 1 9 /l, serum bilirubin < 35 µmol/l, creatinine clearance 5ml/min, clinically acceptable haemoglobin levels (max 5 weeks before randomisation) 8. Mentally and physically fit for chemapy as judged by the oncologist 9. Adequate potential for followup 1. Written informed consent

2 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN RANDOMISATION FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F1 (Page of 3), version. 1/8/ EXCLUSION CRITERIA: All must be No wise patient is t eligible Yes No 1. Extensive growth into cranial part of the sacrum (above S3) or the lumbosacral nerve roots indicating that surgery will never be possible even if substantial tumour downsizing is seen. Familial Adematosis Polyposis coli (FAP), Hereditary NonPolyposis Colorectal Cancer (HNPCC), active Crohn s disease or active ulcerative Colitis 3. Concomitant malignancies, except for adequately treated basocellular carcima of the skin or in situ carcima of the cervix uteri. Subjects with prior malignancies must be diseasefree for at least 5 years 4. Kwn DPD deficiency 5. Any contraindications to MRI (e.g. patients with pacemakers) 6. Medical or psychiatric conditions that compromise the patient s ability to give informed consent 7. Presence of metastatic disease or recurrent rectal tumour. 8. Concurrent uncontrolled medical conditions 9. Previous radiapy in the pelvic region (e.g. prostate) or previous rectal surgery (e.g. TEM) or any investigational treatment for rectal cancer within the past month. 1. Pregnancy or breast feeding 11. Kwn malabsorption syndromes or a lack of physical integrity of the upper gastrointestinal tract 1. Clinically significant (i.e. active) cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac dysrhythmia, e.g. atrial fibrillation, even if controlled with medication) or myocardial infarction within the past 1 months 13. Any symptoms or history of peripheral neuropathy

3 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN RANDOMISATION FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F1 (Page 3 of 3), version. 1/8/ SPECIFIC QUESTIONS 1. Written Informed Consent 1. Date of Informed Consent 1. Consent for Tissue Collection yes. Participation in Side Studies 1. Quality of Life (after 3 years) yes. Tumour tissue pre and post treatment yes 3. Serum and Plasma Samples yes 3. Stratification 1. ECOG Performance Status 1. Clinical Tstage ct3 ct4 3. Clinical Nstage cn cn+ 4. Gender male female 5. Baseline MRI Scan yes 1 6. Randomisation 1. Allocated Treatment Arm A: control: 8x1,8 Gy or 5 x, Gy + CT surgery ± CT Arm B: exp.: 5 x 5 Gy CT surgery. Date of Randomisation 1 Notes: Signature Datacenter Signature Investigator Name Name Date Date

4 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN HISTORY AND STAGING FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F (Page 1 of ), version 1.6, 15/11/13 7 x x History and Physical Examination 1. Family History of Bowel Cancer yes. History of Ischaemic Heart Disease yes 3. History of Diabetes Mellitus yes 4. ECOG Performance Status 5. Height [cm] 6. Weight [kg]. Prior Treatment 1. Defunctioning stoma/bypass surgery yes. Other surgery yes 3. Diagsis 1. Date of biopsy taken. Biopsy obtained by endoscopy surgery radiology guided procedure 3. Number Histology Biopsy 4. Adecarcima yes 1 4. Staging 1. Tumour Palpable by Digital Rectal Examination 1. Distance from Anal Verge [mm]. Distance from Anal Verge by Endoscopy [mm] 3. Imaging, Histology, Staging reviewed in Multi Disciplinary Team Meeting 1. Date of MDT yes yes 1

5 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN HISTORY AND STAGING FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F (Page of ), version 1.6, 15/11/13 7 x x Hematology Value Unit 1. Date of Hematology Tests 1 t done. Hemoglobin t done done. mmol/l g/dl 3. Leucocytes t done done. x 1 9 /L 4. Neutrophils t done done. x 1 9 /L 5. Trombocytes t done done x 1 9 /L 6. Biochemistry 1. Date of Biochemistry Tests 1 t done. Creatinin t done done µmol/l mg/dl 3. Alkaline Phosphatase t done done. U/L µkat/l 4. ALAT t done done. U/L µkat/l 5. ASAT t done done. U/L µkat/l 6. Total Bilirubin t done done. µmol/l mg/dl 7. CEA t done done. µg/l = ng/ml Notes: Signature Investigator Name Date

6 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN BASELINE RADIOLOGY FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F3 (Page 1 of ), version.1, 1/7/14 7 x x MRI ASSESSMENT According to the protocol TNM5 has to be used in this trial except for tification of metastatic disease 1. MRI Sagittal Assessment t done done. Scan Record Number 3. Tumour Position in Relation to Peritoneal Reflection above at below 1 4. Distance from Anal Verge [mm] 5. Distance from Arectal junction (mm) 6. Length (L) of tumour [mm] 7. Minimum distance to mesorectal fascia [mm] 8. Location % of circumference 9. MRI ctstage according to TNM5 ct1 ct ct3ab ( 5mm extramural) ct3cd (>5mm extramural) ct4a ( organs/structures) ct4b (peritoneum) 1. Extramural Vascular Invasion yes 11. Tumours below the level of the levators yes 1. cnstage according to TNM5 cn ( LN) cn (benign LN) cn1 (1 to 3 des) cn (4 or more des) 13. Malignant lateral des present, > 1cm (lat N+) or morphological features 14. Sites with distant metastases according to TNM7 M ( metastases) yes M1a (single metastatic site) M1b (multiple metastatic sites)

7 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN BASELINE RADIOLOGY FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F3 (Page of ), version.1, 1/7/14 7 x x 1 9. CT ASSESSMENT 1. CT Assessment t done done. Sites Imaged [tick all that apply] chest abdomen pelvis 3. Positive Lymph Nodes yes 1. Pelvic yes indeterminate. Inguinal yes indeterminate 3. Abdominal yes indeterminate 4. Other yes indeterminate 4. Distant Metastasis yes 1. Liver yes indeterminate. Lung yes indeterminate 3. Other yes indeterminate 1 Notes: Signature Investigator Name Date

8 Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy RADIOTHERAPY FORM Phone: , Fax: CKS RAPIDO CRF: F4 (Page 1 of 1), version.1, 15/11/13 7 x x Radiapy Administered to 1.1 yes to Reason Radiapy poor PS PD dead refusal adm. difficulty immediate surgery. Date of Start Radiapy 3. Date of Stop Radiapy Technique 3DCRT IMRT, specify 5. Full Bladder yes 6. Position prone supine 7. Belly Board or Similar Device used yes 8. Field reduction (arm A) yes (arm B:5X5Gy). Schedule 1. Number of fractions. Fraction dose [Gy]. 3. Boost given yes 3a. Date of boost 1 3b. Number of fractions boost 3c. Fraction dose boost [Gy]. 4. Total dose (incl. boost) [Gy]. 3 Adverse events (CTC grade I ) yes fill out AE form Notes: Signature Investigator Name Date

9 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R PREOPERATIVE CAPECITABINE FORM ARM A P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5a (Page 1 of ), version 1.7, 15/1/14 7 x x CHEMOTHERAPY yes go to Reason chemapy t fit for chemapy patient refusal. CAPECITABINE week 1 week week 3 week 4 week 5 week6 1. Date of first tablets cycle Weight at start [kg] 3. ECOG Performance at start 4. Dose per day [mg] Cumulative dose per week [mg] Interruption current week [days] Dose Modification Relative to Previous week 5% Delay next cycle [days] (if, please fill in ) Reason delay / dose poor compl. poor compl. poor compl. poor compl. poor compl. poor compl. adjustment disease rel. disease rel. disease rel. disease rel. disease rel. disease rel. adm. diff. adm. diff. adm. diff. adm. diff. adm. diff. adm. diff. 1. Date of last tablets % 5% 5% 5%

10 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R PREOPERATIVE CAPECITABINE FORM ARM A P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5a (Page of ), version 1.7, 15/1/14 7 x x ADVERSE EVENTS week 1 week week 3 week 4 week 5 week 6 1. Toxicity (CTC grade 1) 4. LAB TESTS before week 1 before week before week 3 before week 4 before week 5 before week 6 1. Date Laboratory Tests Other unit Hemoglobin mmol/l mg/dl Platelet Count x 1 9 /L 4. WBC x 1 9 /L Neutrophils x 1 9 /L Notes: SIGNATURE Investigator NAME DATE

11 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R PREOPERATIVE CAPOX FORM ARM B P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5b (Page 1 of 3), version 1.7, 15/1/14 7 x x CHEMOTHERAPY yes go to Reason Chemapy t fit for chemapy patient refusal. CAPECITABINE cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 1. Date of first tablets cycle Weight at start [kg] 3. ECOG Performance at start 4. Dose per day [mg] 5. Cumulative dose per cycle [mg] 6. Interruption current cycle [days] 7. Dose Modification Relative to 5% 5% 5% 5% 5% Previous Cycle 8. Delay next cycle [days] (if, please fill in ) 9. Reason delay / dose adjustment poor compl. disease rel. adm. diff. poor compl. disease rel. adm. diff. poor compl. disease rel. adm. diff. poor compl. disease rel. adm. diff. poor compl. disease rel. adm. diff. poor compl. disease rel. adm. diff. 1. Date of last tablets

12 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R PREOPERATIVE CAPOX FORM ARM B P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5b (Page of 3), version 1.7, 15/1/14 7 x x OXALIPLATIN cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 1. Date of Infusion Total Dose [mg] 5. Dose Modification Relative to Previous Cycle 4% 4% 4% 4% 4% 6. Delay next cycle [days] (if, please fill in ) 4. ADVERSE EVENTS cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 1. Toxicity (CTC grade 1)

13 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R PREOPERATIVE CAPOX FORM ARM B P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5b (Page 3 of 3), version 1.7, 15/1/14 7 x x LAB TESTS before cycle 1 before cycle before cycle 3 before cycle 4 before cycle 5 before cycle 6 1. Date Laboratory Tests Other unit Hemoglobin mmol/l mg/dl Platelet Count x 1 9 /L 4. WBC x 1 9 /L Neutrophils x 1 9 /L Notes: SIGNATURE Investigator NAME DATE

14 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R POSTOPERATIVE CAPOX FORM ARM A P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5c (Page 1 of 3), version 1.7, 15/1/14 7 x x CHEMOTHERAPY yes go to Reason Chemapy t fit for chemapy patient refusal. CAPECITABINE cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 cycle 7 cycle 8 1. Date of first tablets cycle Weight at start [kg] 3. ECOG Performance at start 4. Dose per day [mg] Cumulative dose per cycle [mg] Interruption current cycle [days] Dose Modification Relative to Previous Cycle 5% 5% Delay next cycle [days] (if, please fill in ) Reason delay / dose poor compl. poor compl. poor compl. poor compl. poor compl. poor compl. poor compl. poor compl. adjustment disease rel. disease rel. disease rel. disease rel. disease rel. disease rel. disease rel. disease rel. adm. diff. adm. diff. adm. diff. adm. diff. adm. diff. adm. diff. adm. diff. adm. diff. 1. Date of last tablets % 5% 5% 5% 5%

15 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R POSTOPERATIVE CAPOX FORM ARM A P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5c (Page of 3), version 1.7, 15/1/14 7 x x OXALIPLATIN cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 cycle 7 cycle 8 1. Date of Infusion Total Dose [mg] Dose Modification Relative to Previous Cycle 4% 4% Delay next cycle [days] (if, please fill in ) 4. ADVERSE EVENTS 4% cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 cycle 7 cycle 8 4% 4% 4% 4% 1. Toxicity (CTC grade 1) yes AE form yes AE form yes AE form yes AE form yes AE form yes AE form yes AE form yes AE form

16 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R POSTOPERATIVE CAPOX FORM ARM A P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5c (Page 3 of 3), version 1.7, 15/1/14 7 x x LAB TESTS cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 cycle 7 cycle 8 1. Date Laboratory Tests Hemoglobin mmol/l mg/dl Platelet Count x1 9 /L 4. WBC x1 9 /L Neutrophils x1 9 /L Notes: SIGNATURE Investigator NAME DATE

17 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R PREOPERATIVE FOLFOX4 FORM ARM B P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5d (Page 1 of 7), version 1.8, 1/8/14 7 x x 1 9 Only fill out this form in case FOLFOX4 was given as alternative for CAPOX 1. CHEMOTHERAPY yes go to Reason Chemapy t fit for chemapy patient refusal. OXALIPLATIN cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 1. Date of Infusion Weight at start [kg] 3. ECOG Performance at start 4. Total Dose Oxaliplatin [mg] 5. Dose Modification Relative to Previous Cycle 5% 5% 5% 5% 5% 6. Delay next cycle [days] (if, please fill in ) 7. Reason delay / dose adjustment

18 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R PREOPERATIVE FOLFOX4 FORM ARM B P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5d (Page of 7), version 1.8, 1/8/14 7 x x 1 9 Only fill out this form in case FOLFOX4 was given as alternative for CAPOX 3. LEUCOVORIN cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 1. Date of Infusion day Dose per day leucovorin [mg] 5. Cum. dose leucovorin per cycle [mg] 6. Interruption current cycle [days] 7. Dose Modification Relative to Previous Cycle 5% 5% 5% 5% 5% 8. Delay next cycle [days] (if, please fill in ) 9. Reason delay / dose adjustment

19 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R PREOPERATIVE FOLFOX4 FORM ARM B P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5d (Page 3 of 7), version 1.8, 1/8/14 7 x x FU Only fill out this form in case FOLFOX4 was given as alternative for CAPOX cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 1. Date of Infusion day Dose per day 5FU [mg] 5. Cum. dose per cycle 5FU [mg] 6. Interruption current cycle [days] 7. Dose Modification Relative to Previous Cycle 5% 5% 5% 5% 5% 8. Delay next cycle [days] (if, please fill in ) 9. Reason delay / dose adjustment

20 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R PREOPERATIVE FOLFOX4 FORM ARM B P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5d (Page 4 of 7), version 1.8, 1/8/14 7 x x ADVERSE EVENTS Only fill out this form in case FOLFOX4 was given as alternative for CAPOX cycle 1 N.A cycle N.A cycle 3 N.A cycle 4 N.A cycle 5 N.A cycle 6 N.A 1. Toxicity (CTC grade 1) 6. LAB TESTS before cycle 1 before cycle before cycle 3 before cycle 4 before cycle 5 before cycle 6 1. Date Laboratory Tests Other unit Hemoglobin mmol/l mg/dl Platelet Count x 1 9 /L 4. WBC x 1 9 /L Neutrophils x 1 9 /L......

21 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R PREOPERATIVE FOLFOX4 FORM ARM B P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5d (Page 5 of 7), version 1.8, 1/8/14 7 x x OXALIPLATIN Only fill out this form in case FOLFOX4 was given as alternative for CAPOX cycle 7 N.A cycle 8 cycle 9 1. Date of Infusion Weight at start [kg] 3. ECOG Performance at start 4. Total Dose Oxaliplatin [mg] Dose Modification Relative to Previous Cycle 5% 5% 5% Delay next cycle [days] (if, please fill in ) Reason delay / dose adjustment

22 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R PREOPERATIVE FOLFOX4 FORM ARM B P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5d (Page 6 of 7), version 1.8, 1/8/14 7 x x 1 9 Only fill out this form in case FOLFOX4 was given as alternative for CAPOX 8. LEUCOVORIN 9. 5FU cycle 7 N.A cycle 8 cycle 9 cycle 7 cycle 8 cycle Date of Infusion day Dose per day [mg] Cum. dose per cycle [mg] Interruption current cycle [days] 5% 5% N.A 5% disease rel. Dose Modification Relative to Previous Cycle 5% 5% 5% Delay next cycle [days] (if, please fill in ) Reason delay / dose adjustment

23 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R PREOPERATIVE FOLFOX4 FORM ARM B P.O. Box 96, 3 RC LEIDEN datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5d (Page 7 of 7), version 1.8, 1/8/14 7 x x ADVERSE EVENTS Only fill out this form in case FOLFOX4 was given as alternative for CAPOX cycle 7 N.A cycle 8 cycle 9 1. Toxicity (CTC grade 1) 11. LAB TESTS before cycle 7 before cycle 8 before cycle 9 1. Date Laboratory Tests Other unit Hemoglobin mmol/l mg/dl Platelet Count x 1 9 /L.. 4. WBC x 1 9 /L Neutrophils x 1 9 /L..... Notes: SIGNATURE Investigator NAME DATE

24 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN POSTOPERATIVE FOLFOX4 FORM ARM A datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5e (Page 1 of 8), version 1.7, 1/7/14 7 x x 1 9 Only fill out this form in case FOLFOX4 was given as alternative for CAPOX 1. CHEMOTHERAPY yes go to Reason Chemapy t fit for chemapy patient refusal. OXALIPLATIN cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 1. Date of Infusion Weight at start [kg] 3. ECOG Performance at start 4. Total Dose Oxaliplatin [mg] 5. Dose Modification Relative to Previous Cycle 5% 5% 5% 5% 5% 6. Delay next cycle [days] (if, please fill in ) 7. Reason delay / dose adjustment

25 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN POSTOPERATIVE FOLFOX4 FORM ARM A datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5e (Page of 8), version 1.7, 1/7/14 7 x x 1 9 Only fill out this form in case FOLFOX4 was given as alternative for CAPOX 3. LEUCOVORIN cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 1. Date of Infusion day Dose per day leucovorin [mg] 5. Cum. dose leucovorin per cycle [mg] 6. Interruption current cycle [days] 7. Dose Modification Relative to Previous Cycle 5% 5% 5% 5% 5% 8. Delay next cycle [days] (if, please fill in ) 9. Reason delay / dose adjustment

26 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN POSTOPERATIVE FOLFOX4 FORM ARM A datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5e (Page 3 of 8), version 1.7, 1/7/14 7 x x 1 9 Only fill out this form in case FOLFOX4 was given as alternative for CAPOX 4. 5FU cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 1. Date of Infusion day Dose per day 5FU [mg] 5. Cum. dose per cycle 5FU [mg] 6. Interruption current cycle [days] 7. Dose Modification Relative to Previous Cycle 5% 5% 5% 5% 5% 8. Delay next cycle [days] (if, please fill in ) 9. Reason delay / dose adjustment

27 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN POSTOPERATIVE FOLFOX4 FORM ARM A datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5e (Page 4 of 8), version 1.7, 1/7/14 7 x x 1 9 Only fill out this form in case FOLFOX4 was given as alternative for CAPOX 5. ADVERSE EVENTS cycle 1 cycle cycle 3 cycle 4 cycle 5 cycle 6 1. Toxicity (CTC grade 1) 6. LAB TESTS before cycle 1 before cycle before cycle 3 before cycle 4 before cycle 5 before cycle 6 1. Date Laboratory Tests Other unit Hemoglobin mmol/l mg/dl Platelet Count x 1 9 /L.. 4. WBC x 1 9 /L Neutrophils x 1 9 /L......

28 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN POSTOPERATIVE FOLFOX4 FORM ARM A datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5e (Page 5 of 8), version 1.7, 1/7/14 7 x x OXALIPLATIN Only fill out this form in case FOLFOX4 was given as alternative for CAPOX cycle 7 N.A cycle 8 cycle 9 cycle 1 cycle 11 cycle 1 1. Date of Infusion day Weight at start [kg] 3. ECOG Performance at start 4. Total Dose Oxaliplatin [mg] 5. Dose Modification Relative to Previous Cycle 5% 5% 5% 5% 5% 5% 5% 6. Delay next cycle [days] (if, please fill in ) 7. Reason delay / dose adjustment

29 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN POSTOPERATIVE FOLFOX4 FORM ARM A datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5e (Page 6 of 8), version 1.7, 1/7/14 7 x x 1 9 Only fill out this form in case FOLFOX4 was given as alternative for CAPOX 8. LEUCOVORIN cycle 7 N.A cycle 8 cycle 9 cycle 1 cycle 11 cycle 1 1. Date of Infusion day Dose per day leucovorin [mg] 5. Cum. dose leucovorin per cycle [mg] 6. Interruption current cycle [days] Dose Modification Relative to Previous Cycle Delay next cycle [days] (if, please fill in ) 9. Reason delay / dose adjustment 5% 5% 5% 5% 5% 5%

30 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN POSTOPERATIVE FOLFOX4 FORM ARM A datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5e (Page 7 of 8), version 1.7, 1/7/14 7 x x 1 9 Only fill out this form in case FOLFOX4 was given as alternative for CAPOX 9. 5FU cycle 7 N.A cycle 8 cycle 9 cycle 1 cycle 11 cycle 1 1. Date of of Infusion day Dose per day 5FU [mg] 5. Cum. dose per cycle 5FU [mg] 6. Interruption current cycle [days] Dose Modification Relative to Previous Cycle Delay next cycle [days] (if, please fill in ) 9. Reason delay / dose adjustment 5% 5% 5% 5% 5% 5%

31 course radiation therapy followed by prolonged preoperative chemapy and surgery in patients with high risk primary rectal cancer compared to standard preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN POSTOPERATIVE FOLFOX4 FORM ARM A datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F5e (Page 8 of 8), version 1.7, 1/7/14 7 x x 1 9 Only fill out this form in case FOLFOX4 was given as alternative for CAPOX 1. ADVERSE EVENTS cycle 7 N.A cycle 8 cycle 9 cycle 1 cycle 11 cycle 1 1. Toxicity (CTC grade 1) 11. LAB TESTS before cycle 7 before cycle 8 before cycle 9 before cycle 1 before cycle 11 before cycle 1 1. Date Laboratory Tests Other unit Hemoglobin mmol/l mg/dl Platelet Count x 1 9 /L.. 4. WBC x 1 9 /L Neutrophils x 1 9 /L Notes: SIGNATURE Investigator NAME DATE

32 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN RESTAGING RADIOLOGY FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F6 (Page 1 of ), version.1, 1/7/14 7 x x MRI ASSESSMENT According to the protocol TNM5 has to be used in this trial except for tification of metastatic disease 1. MRI Sagittal Assessment t done done. Scan Record Number 3. Tumour Position in Relation to Peritoneal Reflection above at below tumour Tumour / fibrosis 4. Distance from Anal Verge [mm] tumour 5. Distance from Arectal junction [mm] tumour 6. Residual tumour visible yes 7. Fibrosis visible yes 8. Length (L) of tumour/fibrosis[mm] 9. Minimum distance to mesorectal fascia [mm] 1. Location of tumour from % of circumference 11. MRI ctstage according to TNM5 ct ct1 ct ct3ab ( 5mm extramural) 1. Extramural Vascular Invasion yes 13. Tumours below the level of the levators yes 14. cnstage according to TNM5 cn ( LN) ct3cd (>5mm extramural) cn (benign LN) ct4a ( organs/structures) cn1 (1 to 3 des) 1 ct4b (peritoneum) cn (4 or more des) 15. Malignant lateral des present, > 1cm (lat N+) or morphological features yes 16. Sites with distant metastases according to TNM7 M ( metastases) M1a (single metastatic site) M1b (multiple metastatic sites)

33 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN RESTAGING RADIOLOGY FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F6 (Page of ), version.1, 1/7/14 7 x x 1 9. CT ASSESSMENT 1. CT Assessment t done done. Sites Imaged [tick all that apply] chest abdomen pelvis 3. Positive Lymph Nodes yes 1. Pelvic yes indeterminate. Inguinal yes indeterminate 3. Abdominal yes indeterminate 4. Other yes indeterminate 4. Distant Metastasis yes 1. Liver yes indeterminate. Lung yes indeterminate 3. Other yes indeterminate 1 Notes: Signature Investigator Name Date

34 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN SURGERY FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F7 (Page 1 of 1), version 1.6, 15/11/13 7 x x PREOPERATIVE ASSESSMENTS 1. Date of Assessment. Weight [kg] 3. ECOG Performance Status 4. Surgery offered yes 1. Reason Surgery Offered t fit for surgery patient refused died before surgery. SURGERY 1 1. Date of Surgery. Name Surgeon 1 3. Operating Surgeon consultant registrar 4. Assisting Surgeon consultant registrar robot assistant 5. Duration Surgery [hrs.min]. until. 6. Timing of Surgery elective emergency 7. Metastatic disease at laparotomy yes 1. Location Metastatic Disease locoregional distant 8. Type of Operation laparoscopic complete laparoscopic converted to open 9. Type of Resection resection anterior resection, PME LAR, TME Hartmann APR local excision 1. Intention curative palliative open TEM 11. Intra Operative Radio Therapy (IORT) yes. Gy 1. Stoma yes, defunctioning yes, permanent 13. Mesorectum assessment by surgeon intact breached 14. Margin involvement assessed by surgeon doubtful obvious 15. Blood loss [ml] Notes: Signature Investigator Name Date

35 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN POST SURGERY FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F8 (Page 1 of ), version 1.5, 1/1/1 7 x x POSTOPERATIVE COMPLICATIONS (according to Clavien) I. Infections within 3 days after Surgery 1. Pneumonia yes. Sepsis yes 3. Other yes grade I II IIIa IIIb IVa IVb V II. Cardiovascular 4. Infarction yes 5. Heart failure yes 6. Arrhythmia yes 7. DVT yes 8. Other yes III. Neurologic 9. CVL yes 1. Other yes IV. Surgical 11. Wound Infection yes 1. Intraabdominal infection yes 13. Wound Dehiscence yes 14. Rectal Anastomotic Leak yes 15. Stoma complication yes 16 Ileus yes 17 Gastroparese yes 18. Other yes V. Other yes

36 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN POST SURGERY FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F8 (Page of ), version 1.5, 1/1/1 7 x x 1 9. DISCHARGE / READMISSION / REOPERATION 1. Date of First Discharge 1. Unplanned readmission to hospital [within 3 days since surgery] yes 1 1. Reason(s) Readmission a. Wound rupture yes b. Bleeding yes c. Infection yes d. Rectal anastomotic leak yes e. Other yes. Date of Second Discharge 1 3. Reoperation during first or second admission yes 1 1. Reason(s) Reoperation a. Wound rupture yes b. Bleeding yes c. Infection yes d. Rectal anastomotic leak yes e. Other yes 4. Poerative Mortality yes 1 Notes: Signature Investigator Name Date

37 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN PATHOLOGY FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F9 (Page 1 of ), version 1.8, 15/1/13 7 x x 1 9 According to the protocol TNM5 has to be used in this trial. Countries using TNM7 (i.e. Sweden) are asked to answer questions with both TNM5 and TNM7. 1. Macroscopic Assessment 1. Pathology Number. Surgical plane mesorectal intramesorectal muscularis propria 3. Anal Canal plane outside levator plane sphincter plane intramuscular/submucosal plane ( APR) 4. Tumour to Peritoneal Reflection above at below tumor 5. Length of Tumour [mm] tumor. Histology 1. Tumour Type adeca tumor. Differentiation Grade well moderate poor tumor 3. yptstage according to TNM5 ypt yptis ypt1 ypt ypt3a ypt3b ypt3c ypt3d ypt4a ( organs/ structures) ypt4b (peritoneum) 4. yptstage according to TNM7 ypt yptis ypt1 ypt ypt3a ypt3b ypt3c ypt3d ypt4a (peritoneum) ypt4b ( organs/ structures) 5. ypnstage according to TNM5 ypn ( LN) ypn (benign LN) ypn1 (1 to 3 des) ypn (4 or more des) 6. ypnstage according to TNM7 ypn ( LN) ypn (benign LN) ypn1a (1 regional de) ypn1b (3 des) ypn1c (small tumor deposits) ypna (46 des) ypnb (7 or more des)

38 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN PATHOLOGY FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F9 (Page of ), version 1.8, 15/1/13 7 x x Pathological Response regression regression pcr Tumour Mucin 1. Maximum Extramural Spread [mm] tumor mucin 11 Minimum Distance to distal margin [mm] tumor mucin 1. Minimum Distance to CRM [mm] tumor mucin 13. Type of Margin Involvement direct tumour satellite dal vascular 14. Extramural Vascular Invasion yes 16. Number of Examined Lymph Nodes 17. Number of Positive LN 19. Extradal deposits < 3 mm yes. Macroscopic pictures of tumour yes 1. Tissue fixation 48 hours 4 hours Other: Notes: Signature Investigator Name Date

39 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN FOLLOWUP FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F11 (Page 1 of 1), version 1.5, 15/11/13.. MONTHS POST SURGERY 7 x x Visit t done done 1. Weight [kg]. ECOG Performance Status. CEA Measurement t done done 1. Result CEA. µg/l=ng/ml 3. CT or US liver t done done 1. Result CT or US liver rmal suspect metastases 4. Xray or CT thorax t done done 1. Result thorax investigation rmal suspect metastases 5. Total Coloscopy t done done 1. Result Coloscopy 6. Adverse Events since previous visit? 7. SAE yes SAE form 8. Reoperation yes 1. Reason Reoperation ileus anastomotic leakage tumour recurrence 9. Overall Assessment disease free kwn recurrence new recurrence recurrence form Notes: Signature Investigator Name Date

40 chemapy and surgery in patients with preoperative hemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN FOLLOWUP FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F11 (Page 1 of 1), version 1.5, 15/11/13 6 MONTHS POST SURGERY 7 x x Visit t done done 1. Weight [kg]. ECOG Performance Status. CEA Measurement t done done 1. Result CEA. µg/l=ng/ml 3. Adverse Events since previous visit? 4. SAE yes SAE form 5. Reoperation yes 1. Reason Reoperation ileus anastomotic leakage tumour recurrence 6. Overall Assessment disease free kwn recurrence new recurrence recurrence form Notes: Signature Investigator Name Date

41 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN FOLLOWUP FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F11 (Page 1 of 1), version 1.5, 15/11/13 1 MONTHS POST SURGERY 7 x x Visit t done done 1. Weight [kg]. ECOG Performance Status. CEA Measurement t done done 1. Result CEA. µg/l=ng/ml 3. CT or US liver t done done 1. Result CT or US liver rmal suspect metastases 4. Xray or CT thorax t done done 1. Result thorax investigation rmal suspect metastases 5. Total Coloscopy t done done 1. Result Coloscopy 6. Adverse Events since previous visit? 7. SAE yes SAE form 8. Reoperation yes 1. Reason Reoperation ileus anastomotic leakage tumour recurrence 9. Overall Assessment disease free kwn recurrence new recurrence recurrence form Notes: Signature Investigator Name Date

42 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN FOLLOWUP FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F11 (Page 1 of 1), version 1.5, 15/11/13 4 MONTHS POST SURGERY 7 x x Visit t done done 1. Weight [kg]. ECOG Performance Status. CEA Measurement t done done 1. Result CEA. µg/l=ng/ml 3. Adverse Events since previous visit? 4. SAE yes SAE form 5. Reoperation yes 1. Reason Reoperation ileus anastomotic leakage tumour recurrence 6. Overall Assessment disease free kwn recurrence new recurrence recurrence form Notes: Signature Investigator Name Date

43 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN FOLLOWUP FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F11 (Page 1 of 1), version 1.5, 15/11/13 36 MONTHS POST SURGERY 7 x x Visit t done done 1. Weight [kg]. ECOG Performance Status. CEA Measurement t done done 1. Result CEA. µg/l=ng/ml 3. CT or US liver t done done 1. Result CT or US liver rmal suspect metastases 4. Xray or CT thorax t done done 1. Result thorax investigation rmal suspect metastases 5. Total Coloscopy t done done 1. Result Coloscopy 6. Adverse Events since previous visit? 7. SAE yes SAE form 8. Reoperation yes 1. Reason Reoperation ileus anastomotic leakage tumour recurrence 9. Overall Assessment disease free kwn recurrence new recurrence recurrence form Notes: Signature Investigator Name Date

44 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN FOLLOWUP FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F11 (Page 1 of 1), version 1.5, 15/11/13 6 MONTHS POST SURGERY 7 x x Visit t done done 1. Weight [kg]. ECOG Performance Status. CEA Measurement t done done 1. Result CEA. µg/l=ng/ml 3. Total Coloscopy t done done 1. Result Coloscopy 4. Adverse Events since previous visit? 5. SAE yes SAE form 6. Reoperation yes 1. Reason Reoperation ileus anastomotic leakage tumour recurrence 7. Overall Assessment disease free kwn recurrence new recurrence recurrence form Notes: Signature Investigator Name Date

45 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN LOCOREG. RECURRENCE FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F1a (Page 1 of 1), version 1.5, 15/11/13 7 x x Date of LocoRegional Recurrence. Location(s) [tick all that apply] at anastomosis regional LN(s) into bladder into prostate into vagina skin in local area 3. Investigations and Results 1. Cytology/Histology t done negative positive. CT Scan t done rmal suspect 3. MRI Scan t done rmal suspect 4. PET Scan t done rmal suspect 5. CEA t done rmal increased CEA unit: µg/l=ng/ml. 6. Other t done rmal suspect 4. Type of Treatment pall. intent curative intent 1. Surgery yes. Radiapy yes 3. Systemic yes 4. Other yes Notes: Signature Investigator Name Date

46 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN DISTANT RECURRENCE FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F1b (Page 1 of 1), version 1.5, 15/11/13 7 x x Date of Distant Recurrence. Location(s) [tick all that apply] bone brain liver lung skin peritoneal carcimatosis LN paraaortal, retroperitoneal, inguinal, parailiac etc 3. Investigations and Results 1. Cytology/Histology t done negative positive. Bone Scan t done rmal suspect 3. Chest X Ray t done rmal suspect 4. US Liver t done rmal suspect 5. CT Scan t done rmal suspect 6. MRI Scan t done rmal suspect 7. PET Scan t done rmal suspect 8. CEA t done rmal increased CEA unit: µg/l=ng/ml. 9. Other t done rmal suspect 4. Type of Treatment pall. intent curative intent 1. Surgery yes. Radiapy yes 3. Systemic yes 4. Other yes Notes: Signature Investigator Name Date

47 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN NEW PRIMARY TUMOUR FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F1c (Page 1 of 1), version 1.4, 1/3/1 7 x x Date of New Primary Tumour. Location(s) bladder breast colon endometrium lung prostate 3. Investigations and Results 1. Cytology/Histology t done negative positive. Chest X Ray t done rmal suspect 3. US Liver t done rmal suspect 4. CT Scan t done rmal suspect 5. MRI Scan t done rmal suspect 6. PET Scan t done rmal suspect 7. Other t done rmal suspect 4. Type of Treatment pall. intent curative intent 1. Surgery yes. Radiapy yes 3. Systemic yes 4. Other yes Notes: Signature Investigator Name Date

48 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN END OF TREATMENT FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F13 (Page 1 of 1), version 1.8, 1/7/14 7 x x 1 9 Please fill out this form at start of Follow up 1 Date of last Irradiation 1 never started Date of last preop Capecitabine 1 never started [FOLFOX] Date of last preop Oxaliplatin [only arm B] Date of last preop Leucovorin/5FU [only arm B if FOLFOX was given] Date of Surgery Date of last po CAPOX or FOLFOX [optional: only arm A in certain centers] never started [arm A] never started surgery never started [ FOLFOX] Reason for End of Preoperative Treatment [tick only one main category] completed protocol till surgery lack of efficacy [inadequate tumour regression to warrant continuation] disease progression adverse event(s) unrelated incident intolerable sudden/toxic death SAE form + death form self withdrawal patient refused all treatments Arm A: patient refused CRT: immediate surgery Arm B: patient refused RT: immediate surgery Arm B: patient refused RT: only CT and surgery Arm B: patient refused CT: immediate surgery Arm B: patient refused CT: only RT and surgery Other: ncompliance Notes: If chemapy was given for recurrent disease, this is outside protocol and must be ted on recurrence forms (F1). Not on this EOT form (F13) and t on po CAPOX or FOLFOX form (F5c or F5e) Signature Investigator Name Date

49 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN OFF STUDY FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F14 (Page 1 of 1), version 1.4, 1/3/1 7 x x Last Date in Study 1. Reason Off Study patient wish, specify investigator wish, specify death Death Form Notes: Signature Investigator Name Date

50 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN DEATH FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F (Page 1 of 1), version 1.4, 1/3/1 7 x x Date of Death. Autopsy yes Please send autopsy report 3. Cause of Death rectal cancer go to sites of rectal disease second primary malignancy study drug related surgery related / poerative 1. Sites of Rectal Disease local [Tick all that apply] regional (lymph des) lung liver peritonitis carcimatosa distant lymph des bone brain skin Notes: Signature Investigator Name Date

51 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN ADVERSE EVENTS FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F3 (Page 1 of 1), version 1.6, 1/7/14 7 X X 1 9 Instructions: Please complete at baseline, after each cycle and during followup. Use NCI CTCAE version 4. and use in the Grade, if was present. Report the worst grading during each cycle. 1 Modality Radiation Chemoradiation Preop CAPOX Preop FOLFOX4 Po CAPOX Po FOLFOX4 Period baseline week cycle cycle cycle cycle 3 Date of Assessment 1 4. ECOG performance status Toxicities Grade Grade FUP 5. BLOOD AND LYMPHATIC SYSTEM Febrile neutropenia 6. GASTROINTESTINAL Abdominal pain Colonic obstruction Constipation Diarrhea Fecal incontinence Mucositis oral Nausea Proctitis Rectal hemorrhage Rectal mucositis Rectal pain Vomiting 7. GENERAL Fatigue 8. IMMUNE SYSTEM Allergic Reaction 9. INVESTIGATIONS Weight Loss 1. NERVOUS SYSTEM DISORDERS Lethargy Neuralgia Peripheral sensory neuropathy 11. RESPIRATORY, THORACIC AND MEDIASTINAL Laryngopharyngeal dysesthesia 1. RENAL AND URINARY DISORDERS Cystitis ninfective 13. SKIN AND SUBCUTANEOUS TISSUE Alopecia Palmarplantar erythrodysesthesia syndrome Dermatitis radiation Rash maculopapular 14. SEXUAL PROBLEMS 15. OTHER Other 1 Other Other 3 Other SAE observed yes go to SAE form Notes: Signature Investigator Name Date

52 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN SERIOUS ADVERSE EVENT FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F4 (Page 1 of 4), version 1.9, 1/7/14 Please add additional / new information to the initial form! 7 x x Reaction Information 1. Report type initial followup final. Country 3. Age [years] 4. Sex male female 8x1,8 Gy 5. Treatment Arm Arm A control: + CT surgery [:± optional CT] or 5x, Gy Arm B experimental: 5x5 Gy CT surgery 6. Date of onset SAE 7. Onset period of SAE during/shortly after 5x5 Gy during/after preop CRT during/after preop CT surgery postsurgery during/after po CT followup before treatment 8. Description SAE in a single term 9. Intensity SAE [CTC 4.] grade 1 grade grade 3 grade 4 grade 5 1. Category of SAE patient died persistent or sign. disability/incapacity (prolonged) inpatient hospitalisation life threatening congenital amaly or birth defect medically important Date of Death Cause of Death malignant disease 11. Outcome SAE recovered sequelae unchanged worsened fatal Date of recovery SAE. Suspect Drug(s) Information Reaction Information Therapy First date of Last date of duration Study Drugs /Therapy Daily dose Route administration administration [weeks] Radiapy [Gy], 1 1 Capecitabine [Xeloda ] [mg] Oxaliplatin [Eloxatin ] [mg] N.A oral 1 1 N.A i.v. 1 1 Leucovorin [mg] N.A i.v FU [mg] N.A i.v. 1 1

53 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN SERIOUS ADVERSE EVENT FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F4 (Page of 4), version 1.9, 1/7/14 Please add additional / new information to the initial form! 7 x x 1 9 Study Drugs /Therapy Radiapy N.A Causality unrelated unlikely possible probable definite t assessable Did reaction abate after ping? yes. Did reaction reappear after reintroduction? yes Action taken? dose reduced temp. Capecitabine [Xeloda ] N.A unrelated unlikely possible probable definite t assessable yes yes dose reduced temp. Oxaliplatin [Eloxatin ] N.A unrelated unlikely possible probable definite t assessable yes yes dose reduced temp. Leucovorin N.A unrelated unlikely possible probable definite t assessable yes yes dose reduced temp. 5FU N.A unrelated unlikely possible probable definite t assessable yes yes dose reduced temp. Prophylactic Drug(s) Causality 5HT3 antagonist Corticosteroids Tromboembolic prophylaxis unrelated definite unrelated definite unrelated definite unlikely t assessable unlikely t assessable unlikely t assessable possible t administered possible t administered possible t administered probable probable probable

54 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN SERIOUS ADVERSE EVENT FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F4 (Page 3 of 4), version 1.9, 1/7/14 Please add additional / new information to the initial form! 7 x x Concomitant medication yes Generic name and dose Start date Stop date Relevant Medical History

55 chemapy and surgery in patients with preoperative chemoradiapy, surgery and optional adjuvant chemapy Dept. of Surgery, Datacenter, K6R P.O. Box 96, 3 RC LEIDEN SERIOUS ADVERSE EVENT FORM datacenter@lumc.nl Phone: , Fax: CKS RAPIDO CRF: F4 (Page 4 of 4), version 1.9, 1/7/14 Please add additional / new information to the initial form! 7 x x Relevant Laboratory Values 1. Date Laboratory tests t done. Hemoglobin. mmol/l mg/dl 3. Platelet Count x 1 9 /L 4. WBC. x 1 9 /L 5. Neutrophils. x 1 9 /L 6. Other, specify incl unit t done 6. Manufacturer Information Signature: 1. Report source Health professional. Date of initial report 3. Date of follow up report 7. Contact details [person who filled out this form and address] Notes: Signature Investigator Name Date final report