2.1 Patients
This study was carried out in Ayadi Almostakbal Oncology Center during the period from April 2019 to January 2021. Inclusion criteria: any age, histologically confirmed prostatic adenocarcinoma. Low or intermediate risk Localized prostate cancer according to NCCN risk classification. Low-risk patients included cT1c–T2a, N0, M0, Gleason score 6 or less, and prostate-specific antigen (PSA) concentration < 10 ng/mL. Intermediate-risk patients had at least one of the following criteria: T2b-c, Gleason score 7, and PSA 10–20 ng/mL.
Exclusion criteria: T3,4 lesions, extra capsular extension, seminal vesicle invasion, positive lymph node metastasis, Gleason score ≥ 8, risk of pelvic lymph node involvement > 15% by Roch formula, PSA > 20 ng/dl, metastatic disease, inflammatory bowel disease, previous radiotherapy to the pelvis. Unfavourable intermediate risk patients received zoladex for 6 months starting 2 months before radiotherapy.
All patients had pre-treatment staging including a complete history, physical examination, digital rectal examination, trans rectal ultrasound of the prostate, biopsy, prostate-specific antigen (PSA) level and MRI pelvis.
2.2 Methods
Patients were immobilized using body mattress extend from mid back to mid-thigh in the supine positions with hands above the head. Patients were instructed for a low residue diet and to empty the rectum using an enema the night prior to simulation. The anterior posterior diameter of the rectum should be less than 4 cm during simulation. Also, a comfortably full bladder (patients empty urinary bladder then drink 500 ml water and abstain urination for one hour before simulation). Patients were scanned in the treatment position from the L5-S1 level to the mid femur level on a computerized tomography (CT) simulator 3 mm slice thickness. CT simulation films and the pelvic MRI images were fused according to the bony landmarks.
2.3 Delineation of target volume and organs at risk:
CTV: prostate + proximal 1 cm of the proximal seminal vesicle.
PTV = CTV + 0.8 cm except posteriorly 0.5 cm.
An additional 0.7-cm margin was added around the planning target volume (PTV) to account for penumbra.
The rectum defined by the outer rectal wall from the rectosigmoid junction till the anorectal junction, urinary bladder defined by the outer bladder wall, right and left femoral heads, penile pulb and bowel bag were contoured as critical normal tissue structures using the focal system.
2.4 Plan design:
After contouring of the target volumes and organs at risk, the CT images were transferred from focal system to the treatment planning system XiO 4.64 (Computerized Medical Systems, St. Louis, MO, USA) using the superposition algorithm. Three sets of Inverse planning IMRT were carried out using step-and-shoot technique (5 fields, 7 fields and 9 Fields) for each patient. An equidistant fields were generated using 6MV- 15 MV photons and dosimertrically compared regarding target volume coverage and organ at risk sparing. All three plans were done using 6MV – 15MV photons.
IMRT-5: beams were arranged with equal angle separation of 72 degrees between each two beams: 00,720, 1440, 2160 and 2880.
IMRT-7: 51 degrees equal angle separation between each two beams: 00, 510, 1020, 1530, 2040, 2550 and 3060.
IMRT-9: equal angle separation of 40 degrees between each two beams: 00, 400, 800, 1200, 1600, 2000, 2400, 2800, and 3200.
Target volume dosimetric parameters which are considered for comparison between the three planning techniques will be: maximum dose (Dmax), minimum dose (Dmin), mean dose (Dmean), 95% dose (V95%), median dose, homogeneity index (HI), and conformity index (CI) for irradiated tumour volumes.
For both rectum and urinary bladder: V15%, V25%, V35% and V50% were calculated. For right and left femori: maximum (Dmax) and mean dose (Dmean). These dosimetric parameters of the target volume and organs at risk were compared for the 3 sets of IMRT planning.
2.5 Total dose and fractionation:
70 Gy/ 28 fractions, 2.5 Gy/fraction, 5 fractions /week. Daily treatment verification using cone beam CT was done for all patients.
2.6 Dose constrains: Dose constrains for organs at risk are listed in (table 1).
Table (1)
Dose constrains for organs at risk:
Bladder Constraints
|
Rectal Constraints
|
Femoral head
|
Penile pulb
|
Dose
|
<Vol%
|
Dose
|
<Vol%
|
Dose
|
<Vol %
|
|
79 Gy
|
15%
|
74 Gy
|
15%
|
50 Gy
|
2%
|
Mean < 50Gy
|
74 Gy
|
25%
|
69 Gy
|
25%
|
|
|
69 Gy
|
35%
|
64 Gy
|
35%
|
|
|
64 Gy
|
50%
|
59 Gy
|
50%
|
|
2.7 plan evaluation:
Plans were considered acceptable if ≥95% of the PTVs received ≥95% of the prescription dose.
DVHs for the prostate PTV, rectum, bladder and bowel bag were calculated for each patient for the 3 planning techniques.
The conformity index (CI) and homogeneity index (HI) were defined to describe the quality of plans as follows:
CI = Vt ref / V t X Vt ref / V ref
Where Vt represents target volume, Vt,ref represents the target volume wrapped by reference isodose curve face (95%), and Vref represents all the volume wrapped by reference isodose curve (95%). A higher CI value, ranging from 0 –1, represents better conformity.
HI = D2-D98/Dp
Where D2 = dose to 2% of the target volume indicating the “maximum dose”, D98 = dose to 98% of the target volume, indicating the “minimum dose” and Dp = prescribed dose.
Lower HI is indicative of a more homogeneous dose distribution across the PTV.
The total number of MUs per fraction and the treatment time were used to evaluate the efficiency of treatment delivery.
After analysis of the differences between the dosimetric results in the three techniques based on dose-volume histograms (DVHs), the best technique of them will be recommended for the treatment of patients.
2.8 Follow up:
Patients were assessed clinically every other week during radiotherapy and monthly thereafter for 3 months and then every 3 months during follow up.
PSA was measured at base line and every 3 months during the first 2 years. Acute toxicity was defined as an event that developed during radiotherapy or within the first 3 months after the end of treatment. Late toxicity was defined as an event that manifested 3 months after the end of treatment. Acute and late events were graded according to Common Terminology Criteria for Adverse Events version 4.0 [17].
2.9 Statistical analysis:
Data were analyzed using SPSS statistical package version 22. Numerical data were summarized as median, mean and range. The Kruskal Wallis H test was used to determine statistical differences between volumes and doses in 5 field IMRT vs. 7field IMRT vs 9 field plans. The Mann Whitney test was used to determine statistical differences between volumes and doses in 5 field IMRT and 7field IMRT or between 7 field IMRT and 9 field IMRT or 7 field IMRT and 9field IMRT. P-value < 0.05 is considered significant.