Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Conventional arm: primary surgery followed by chemotherapy

Neoadjuvant chemotherapy followed by interval debulking

timing of surgery

Lalit Kumar, DM

To determine the impact of Neoadjuvant chemotherapy on surgical debulking rate, overall and disease-free survival and quality of life (QOL) in patients with advanced EOC.

Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer (EOC): A Phase III Randomized Study

Neoadjuvant Chemotherapy (NACT) Followed by Interval Debulking Surgery vs Upfront Surgery Followed by Chemotherapy (CT) in Advanced Epithelial Ovarian Carcinoma (EOC): A Prospective Randomized Study

All India Institute of Medical Sciences, New Delhi

Prof Lalit Kumar

Digestive System Diseases

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Rectal Diseases

Preoperative radiotherapy (RT) given 5 times 5 Gray during five consecutive days, preferably Monday - Friday, with a four-field box technique, including the primary tumour and the primary and secondary lymph nodes in the pelvis.

Short-course RT

Preoperative radiotherapy (RT) given 2 Gy in 25 fractions during 5 weeks, total dose 50 Gy with a four-field box technique, including the primary tumour and the primary and secondary lymph nodes in the pelvis.

Long-course RT

Anna Martling, Professor

Preoperative radiotherapy (RT) is recommended to many patients with localised rectal cancer, not previously treated with pelvic RT. However, the optimum fractionation, the timing of surgery and the best use of concomitant chemotherapy remains controversial. There are theoretical reasons to believe that radiotherapy given in larger fractions during a shorter period of time might result in more late side effects than giving a conventional, more protracted RT in patients with rectal cancer. In addition, the optimum timing of surgery after RT, with respect to postoperative morbidity, mortality and potential downsizing of the tumour is not known.

To address these questions, a prospective randomized multicenter trial was initiated, the Stockholm III trial, in which patients with primarily resectable rectal cancer were randomized to short-course preoperative RT (5x5 Gy) followed by surgery within one week or after 4-8 weeks or long-course preoperative RT(25x2 Gy) followed by surgery after 4-8 weeks.

840 participants (men and women) with a biopsy verified adenocarcinoma of the rectum scheduled for an open abdominal procedure were enrolled at 18 Swedish Hospitals during 1998-2013.

In the initial protocol patients were randomly assigned (1:1:1) between three different RT courses; 5x5 Gy with surgery within 1 week (SRT), 5x5 Gy with surgery after 4-8 weeks (SRT-delay) or 25x2 Gy during 5 weeks without concomitant chemotherapy and surgery after 4-8weeks (LRT-delay). After a protocol amendment on May 21, 1999, participating hospitals could choose to randomise patients to just the short-course radiotherapy arms (1:1) or to all three arms.

Randomisation was done by telephone by the Regional Cancer Centre in Stockholm, Sweden, after assessing inclusion and exclusion criteria. Computer generated randomisation lists were constructed by use of permuted block technique (block size of six for the three- arm randomisation, block size of four for the two-arm randomisation) and stratified by participating center. Investigators and patients were not masked to treatment.

Follow-up was recommended at 3-, 6- and 12 months after surgery, and yearly thereafter. Although follow-up according to national guidelines with a minimum follow-up at 1 and 3 years was allowed. Patient data was also collected from the Swedish ColoRectal Cancer Register (SCRCR) and medical records.

Primary outcome:

1. Time to local recurrence.

Secondary outcomes:

1. Recurrence-free survival
2. Frequency of postoperative complications
3. Frequency of tumour regression

The Stockholm III Trial on Different Preoperative Radiotherapy Regimens in Rectal Cancer

A Prospective Randomized Trial on Different Preoperative Radiotherapy Regimens in Rectal Cancer, Stockholm III.

Local recurrence was defined as tumour growth below the level of the sacral promontory, related to the previous rectal cancer, and diagnosed radiographically with MRI, CT, or both, or clinically (preferably with histological confirmation). A diagnosis of local recurrence was confirmed and reported by the patient-responsible physician to the Swedish ColoRectal Cancer Registry (SCRCR), a nationwide validated national registry. Local recurrence was measured both as first and any event occurring during follow-up (censoring date March 30 2015), when all patients had been followed for at least 2 years.

Postoperative complications was defined as any cardiovascular event, infectious, neurological or surgical complications occurring within 30 days after surgery, or during the same hospital admission, validated from medial records. Overall postoperative complication was defined as having at least one postoperative complication. Participants were grouped based on type of preoperative radiotherapy (RT) regimen (eg short- or long course) and overall treatment time (OTT), defined as time between start of RT and surgery. Participants receiving short-course RT were categorised into four different groups; Group A: OTT 7 days, Group B: OTT 8-13 days, Group C: OTT 5-7 weeks, Group D: OTT 8-13 weeks. Participants receiving long-course RT were categorised into two different groups; Group E: OTT 9-11 weeks, Groups F: OTT 12-14 weeks.

Tumour regression (TRG) was assessed using the Dworak grading scoring system, ranging from scores 0 to 4 with higher scores indicating better tumour regression. Definition of scores; 0 = no regression, 1 = dominant tumour mass with obvious fibrosis and/or vasculopathy, 2 = dominantly fibrotic changes with few tumour cells or groups (easy to find), 3 = very few (difficult to find microscopically) tumour cells in fibrotic tissue with or without mucous substance, 4 = no tumour cells, only fibrotic mass (total regression or complete response). All available microscopy slides were assessed by one pathologist, blinded to treatment.

Swedish Cancer Society

The Swedish Research Council

Karolinska Institutet

Professor, Senior Consultant Surgeon

Serious adverse events: Acute radiation-induced toxicity was not assessed in such manner that specific terms can be separated.

Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.

Three-arm Randomisation: SRT

Participants included in the three-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.

Three-arm Randomisation: SRT-delay

Participants included in the three-armed randomisation and allocated to long-course preoperative radiotherapy (25x5 Gy) and surgery after 4-8 weeks.

Three-arm Randomisation: LRT-delay

Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week pooled from both three-armed and two-armed randomisation.

Pooled Short-course RT: SRT

Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks pooled from both three-armed and two-armed randomisation.

Pooled Short-course RT: SRT-delay

Participants included in the two-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.

Two-arm Randomisation: SRT

Participants included in the two-armed randomisation and allocated to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.

Two-arm Randomisation: SRT-delay

Total

Age, Continuous

Sex: Female, Male

0-5 centimeter

6-10 centimeter

11-15 centimeter

Missing

Tumour height from anal verge

Anterior Resection

Abdominal perineal excision

Hartmann's

Local excision

No resection

Type of Surgery

Stage x

Pathological tumour stage after neoadjuvant treatment calculated according to the AJCC 8th edition. Stages ranging from I to IV with higher number indicating more advanced cancer. Stage x = Unknown stage.

ypStage

Anna Martling

The effect of treatment regimen on local recurrence as first event in the three-armed group comparison (n = 385) was estimated with proportional hazards regression, stratified by participating centre.

The effect of treatment regimen on recurrence-free survival in the three armed randomisation comparison (n = 385) was estimated with proportional hazards regression, stratified by participating centre.

The effect of treatment regimen on local recurrence as first event in the pooled short-course RT comparison (n = 712) was estimated with proportional hazards regression, stratified by participating centre.

The effect of treatment regimen on recurrence-free survival in the pooled short-course RT comparison (n = 712) was estimated with proportional hazards regression, stratified by participating centre.

Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week pooled from the three-armed and two-armed randomisation.

Participants assigned to short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks pooled from the three-armed and two-armed randomisation.

Participants were analysed according to intention to treat.

Time to Local Recurrence.

The association between postoperative complications and short-course RT by overall treatment time was assessed using logistic regression analysis.

The association between postoperative complications and long-course RT by overall treatment time was assessed using logistic regression analysis.

Overall postoperative complications

No postoperative complication

Participants treated with short-course preoperative radiotherapy (5x5 Gy) with overall treatment time of 7 days.

Group A: Short-course RT and OTT 7 Days

Participants treated with short-course preoperative radiotherapy (5x5 Gy) with overall treatment time of 8-13 days.

Group B: Short-course RT and OTT 8-13 Days

Participants treated with short-course preoperative radiotherapy (5x5 Gy) with overall treatment time of 5-7 weeks.

Group C: Short-course RT and OTT 5-7 Weeks

Participants treated with short-course preoperative radiotherapy (5x5 Gy) with overall treatment time of 8-13 weeks.

Group D: Short-course RT and OTT 8-13 Weeks

Participants treated with long-course preoperative radiotherapy (25x2 Gy) with overall treatment time 9 -11 weeks.

Group E: Long-course RT and OTT 9-11 Weeks

Participants treated with long-course preoperative radiotherapy (25x2 Gy) with overall treatment time 12 - 14 weeks.

Group F: Long-course RT and OTT 12-14 Weeks

Participants were analysed as treated and grouped based on type of preoperative radiotherapy (RT) and overall treatment time (OTT).

Number of Participants With Postoperative Complications in Relation to Preoperative Radiotherapy Regimen and Overall Treatment Time.

The association between pathological complete response (pCR), eg no signs of viable tumour or metastatic nodes (T0N0) and overall survival (OS) was assessed using Cox-regression model.

TRG 0

TRG 1

TRG 2

TRG 3

TRG 4

Not assessable

Participants treated with short-course preoperative radiotherapy (5x5 Gy) and surgery within 1 week.

Short-course RT: SRT

Participants treated with short-course preoperative radiotherapy (5x5 Gy) and surgery after 4-8 weeks.

Short-course RT: SRT-delay

Participants treated with long-course preoperative radiotherapy (25x5 Gy) and surgery after 4-8 weeks.

Long-course RT: LRT-delay

Participants grouped based on allocated treatment and analysed as-treated. Only participants with available microscopy slides were included in the analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer (EOC): A Phase III Randomized Study	NCT00715286	Ovarian Carcino...	timing of surge... timing of surge...	20 Years - 65 Years	All India Institute of Medical Sciences, New Delhi
The Stockholm III Trial on Different Preoperative Radiotherapy Regimens in Rectal Cancer	NCT00904813	Rectal Cancer	Short-course RT Long-course RT	18 Years -	Karolinska Institutet
Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer (EOC): A Phase III Randomized Study	NCT00715286	Ovarian Carcino...	timing of surge... timing of surge...	20 Years - 65 Years	All India Institute of Medical Sciences, New Delhi

Spots Global Cancer Trial Database for timing of surgery