Know Cancer

or
forgot password

Phase II Clinical Trial: The Effect of Bone Marrow-sparing Intensity-Modulated Radiotherapy (BMS-IMRT) on Reduction Acute Hematologic Toxicity in Gastric and Rectal Cancer Patients Treated With Concurrent Chemotherapy and IMRT


Phase 2
18 Years
75 Years
Open (Enrolling)
Both
Rectal Cancer, Gastric Cancer, Bone Marrow Toxicity, Adverse Effect of Radiation Therapy

Thank you

Trial Information

Phase II Clinical Trial: The Effect of Bone Marrow-sparing Intensity-Modulated Radiotherapy (BMS-IMRT) on Reduction Acute Hematologic Toxicity in Gastric and Rectal Cancer Patients Treated With Concurrent Chemotherapy and IMRT


1、Simulation All patients underwent computed tomography (CT) simulation in the supine
position for gastric cancer patients and The CT scan was obtained from the T4 vertebral body
to L5 cm. Oral contrast and intravenous contrast were administered prior to the CT scan.

All patients underwent computed tomography (CT) simulation in the prone position for rectal
cancer patients with a full bladder and using a belly board to minimize exposure of the
small bowel. Oral contrast and intravenous contrast were administered prior to the CT scan.
A radio-opaque marker was placed at the anal margin. The superior and inferior limits of the
acquired transaxial data (set by the topogram) were the iliac crests and 5 cm inferior to
the anal marker, respectively. Intravenous contrast were administered prior to the CT scan.

2.Radiotherapy and chemotherapy For gastric cancer patients after surgery and
chemotherapy,the 4500 cGy of radiation was delivered in 25 fractions, five days per week,
to the tumor bed, to the regional nodes, and 2 cm beyond the proximal and distal margins of
resection. The tumor bed was defined by preoperative computed tomographic (CT) imaging,
barium roentgenography, and in some instances, surgical clips. Perigastric, celiac,
local paraaortic, splenic, hepatoduodenal or hepatic-portal, and pancreaticoduodenal lymph
nodes were included in the radiation fields. In patients with tumors of the gastroesophageal
junction, paracardial and paraesophageal lymph nodes were included in the radiation fields.
Concurrent chemotherapy regimen is monotherapy with capecitabine 1600mg∙m2 twice a day
(b.i.d.).

For rectal cancer patients before surgery, The rectum was not opacified with barium in order
to avoid contour artifacts. The gross tumor volume (GTV) was generated with the CT scan, MR
scan and endoscopic ultrasonography results. Only a clinical target volume (CTV) was
delineated, encompassing the entire mesorectum, Pararectal nodes were also included,
together with the presacral and promontory nodes (limit to L5-S1 interspace ), and the
internal iliac nodes up to the venous bifurcation. External iliac nodes were not included as
they have not been a site for recurrence in our experience. On the contrary, internal
pudendal nodes were included in the CTV. Organs at risk were also contoured: bladder (with
intravenous contrast), small bowel (with oral contrast) and femoral heads. The small bowel
was contoured on all CT slices where it could be visualized, which was highly variable among
patients. IMRT is given with 5000 cGy in 25 fractions (5 weeks). Concurrent chemotherapy
consists of oxaliplatin (50 mg/m2 ) intravenously over 2 h on days 1, 8, 15, 22 and 29, and
capecitabine (825 mg/m2 twice day) was given orally on each day of radiation.

3. Active bone marrow definition All the patient was scanned in the supine position on a 1.5
T MR scanner. For gastric cancer patients, the images were obtained from the T8 to L4 for
gastric cancer patients. For rectal cancer patients, the images were obtained from the L3-4
interspace to below the ischial tuberosities for rectal cancer patients.

The MR images were subsequently fused with the planning CT scan using commercially available
image fusion software. The interactive mode of the fusion software was used whereby the user
manually translates and rotates the MR scan to produce the best visual overlay of the two
image sets. A mutual information algorithm was then used to perform a fine adjustment. The
CT and MR images (resliced along the planes of the CT scan) were subsequently displayed
side-by-side. BM regions on the T1-weighted images that showed a signal intensity equal to
or slightly higher than that of muscle were contoured as active BM. The range of active BM
was 3cm beyond the upper limit of PTV and 3cm below the lower limit of PTV.


Inclusion Criteria:



All gastric cancer patients had to fulfill the following criteria: histologically
confirmed adenocarcinoma of the stomach, cancer resected without residual disease (R0
gastrectomy), at least a D1 lymph node dissection, a classification as stage II through
III according to the 2009 staging criteria of the American Joint Commission on Cancer, at
least 4 cycles of chemotherapy, age greater than 18 years and less than or equal to 75
years, a performance status of 1 or lower according to Eastern Cooperative Oncology Group
(ECOG) criteria, adequate function of major organs (including cardiac, hepatic, and renal
functions), adequate bone marrow function (hemoglobin>10g/dL; absolute neutrophil count
[ANC]≥2,000/μL; platelet count≥100,000/μL; leukocyte count ≥4,000/μL), a caloric intake
greater than 1,500 kcal/day by oral route, treatment beginning no later than 4 weeks after
the last cycles of chemotherapy (but a delay of 1 week was allowed to permit full
recovery, with restoration of adequate nutritional intake).

All rectal cancer patients with histologically confirmed rectal adenocarcinoma that
involved the distal 12 cm of the rectum without evidence of distant metastases were
eligible. The patients had to have undergone a staging evaluation within 6 weeks before
initiation of the study by endoscopic ultrasonography (US), with evidence of Stage T3 or
T4 tumor and/or evidence of lymph node involvement defined by the presence of at least one
enlarged perirectal lymph node >8 mm in size and sonographically suspicious for
metastasis. No previous RT to the pelvis and no previous chemotherapy for rectal cancer
were allowed. Other inclusion criteria are age greater than 18 years and less than or
equal to 75 years, a performance status of 1 or lower according to Eastern Cooperative
Oncology Group (ECOG) criteria, adequate function of major organs (including cardiac,
hepatic, and renal functions), adequate bone marrow function (hemoglobin>10g/dL; absolute
neutrophil count [ANC]≥2,000/μL; platelet count≥100,000/μL; leukocyte count ≥4,000/μL), a
caloric intake greater than 1,500 kcal/day by oral route.

Exclusion Criteria:

For gastric patients, cases with stage IA or IB (T2aN0) disease (according to the American
Joint Committee on Cancer 2002 staging system), microscopically positive resection margin,
and involvement of M1 lymph node or distant metastases were excluded from the study; prior
abdominal irradiation;

For rectal patients, cases were excluded from the study if they had metastatic rectal
cancer, other tumour types than adenocarcinoma of the rectum; prior pelvic irradiation;

Other key exclusion criteria were: past or concurrent history of neoplasm except
curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix; current
uncontrolled infection; unresolved bowel obstruction or subobstruction; uncontrolled
Crohn's disease or ulcerative colitis; current history of chronic diarrhoea; other
serious illness or medical conditions; contraindication towards study drugs and radiation;
prior radiotherapy, chemotherapy or any targeting therapy; administration of any other
experimental drug under investigation concomitantly or within 4 weeks before eligibility;
and pregnant or lactating patients.

Type of Study:

Observational [Patient Registry]

Study Design:

Observational Model: Cohort, Time Perspective: Prospective

Outcome Measure:

Hematologic toxicity

Outcome Description:

According to the Radiation Therapy Oncology Group acute radiation morbidity scoring criteria, primary endpoints of interest were the white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin (Hgb), and platelet count nadirs and highest grade of each toxicity occurring within 60 days of initiation of concurrent chemoradiotherapy (CRT). For rectal patients, Grade 2-4 leukopenia, neutropenia,anemia, and thrombocytopenia are considered as endpoints. For gastric patients, Grade 3-4 leukopenia, neutropenia,anemia, and thrombocytopenia are considered as endpoints.

Outcome Time Frame:

Within 60 days of initiation of concurrent chemoradiotherapy

Safety Issue:

No

Principal Investigator

Jing Jin, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Authority:

China: Ministry of Health

Study ID:

LC2012B22

NCT ID:

NCT01863420

Start Date:

November 2012

Completion Date:

October 2015

Related Keywords:

  • Rectal Cancer
  • Gastric Cancer
  • Bone Marrow Toxicity
  • Adverse Effect of Radiation Therapy
  • gastric cancer
  • rectal cancer
  • bone marrow toxicity
  • IMRT
  • hematologic toxicity
  • Rectal Neoplasms
  • Stomach Neoplasms

Name

Location