Background: To evaluate the initial experience and clinical utility of first-line adjuvant intensity-modulated whole abdominal radiation therapy (WART) in women with ovarian clear cell cancer (OCCC) referred to an academic center. Methods: Progression-free and overall survival was analyzed in a pragmatic observational cohort study of histologically pure OCCC patients over-expressing HNF-1ß treated between 2013 and end-December 2018. An in-house intensity-modulated WART program was developed from a published pre-clinical model. Radiation dose-volume data was curated to American Association of Physics in Medicine (AAPM) Task Group 263 recommendations. A dedicated database prospectively recorded presenting characteristics and outcomes in a standardized fashion. Results: Five women with FIGO (2018) stage IA to IIIA2 OCCC were treated with first-line WART. Median age was 58 years (range 47–68 years). At diagnosis CA-125 was elevated in 4 cases (median 56 kU/L: range 18.4–370 kU/L) before primary de-bulking surgery. Severe premorbid endometriosis was documented in 3 patients. At a median follow-up of 77 months (range 16–83 mo.), all patients remain alive and progression-free on clinical, biochemical (CA-125), and 18Fluoro-deoxyglucose (FDG) PET/CT re-evaluation. Late radiation toxicity was significant (G3) in 1 case who required a limited bowel resection and chronic nutritional support at 9 months post-WART; 2 further patients had asymptomatic (G2) osteoporotic fragility fractures of axial skeleton at 12 months post-radiation treated with anti-resorptive agents (denosumab). Conclusions: The clinical utility of intensity-modulated WART in OCCC over-expressing HNF-1β was suggested in this small observational cohort study. The hypothesis that HNF-1β is a portent of platinum-resistance and an important predictive biomarker in OCCC needs further confirmation. Curating multi-institutional cohort studies utilizing WART by means of "Big Data" may improve OCCC care standards in the future.
Keywords: Clear cell ovarian cancer; Intensity-modulated radiation therapy; Whole abdominal radiation therapy; Hepatocyte nuclear factor (HNF)
According to the International Agency for Research on Cancer (IARC) GLOBOSCAN 2018 report, ovarian cancer affects mainly younger women (78% cases < 70 years) and has a relatively poor survival with 5-year death rates of over 50 percent [[
Primary cancers of surface-epithelial origin constitute the majority (90%) of ovarian malignancies [[
Ovarian clear cell cancer (OCCC) is the most recently characterized and least common of the epithelial histologies in North American and European women (overall prevalence 4–9.5% [[
Overexpression of the master transcription factor, hepatocyte-nuclear-factor 1beta (HNF-1β) is a diagnostic marker of OCCC. Current evidence suggests that HNF-1β is a major contributory or interactive [[
Recently [[
We describe for the first time the clinical utility of contemporary intensity-modulated WART in a small prospective series of OCCC patients whose phenotypic signature included HNF-1β over-expression. It was hypothesized that modern WART would be a safe and non-futile therapeutic strategy in women predicted to be platinum-resistant.
This study was pre-approved by the Northern Sydney Local Health District (NSLHD) and included patients who had consented to the use of their oncologic and general medical data stored by the Northern Sydney Cancer Center for clinical follow-up and research purposes.
We prospectively assessed and recorded on a dedicated RT database the cancer outcomes and emergent radiation toxicity of all women receiving first-line adjuvant WART following comprehensive primary staging surgery for OCCC over-expressing HNF-1β. Five women were identified with OCCC between January 2013 and end December 2018 and all had prior resection to minimal residual disease by a single gynecologic oncologist (GG). Table 1 summarizes the cohort demographics, tumor characteristics, and International Federation of Gynecology and Obstetrics (FIGO) 2018 staging. All histopathology was re-interpreted by a specialist gynecologic pathology service (CR and DN). WART was recommended for this OCCC cohort after Tumor Board discussion.
Table 1 Patient demographics and staging characteristics
Patient Age (years) [Ca-125] (kU/L) Stage (2018) Follow-up (months) Peritoneal cytology Endometriosis (years) Ascites Uni-lateral or bilateral tumors Maximum weight (gms) 1 68 370 IC1 (T1c1) 83 Negative No No Bilateral 910/194 2 65 167 IIA (T2a) 81 Positive No No Unilateral 347 3 48 18 IIIA2 (T3a2) 77 Positive Yes (25 years) No Unilateral* 75 4 47 48 IA (T1a) 57 Negative Yes (25 years) No Unilateral 369 5 58 56 IC3 (T1c3) 16 Positive Yes (30 years) No Unilateral 111
A diagnosis of classic OCCC was recorded if > 90% of the examined operative specimen demonstrated typical histo-morphological features, such as cells with abundant clear to granular eosinophilic cytoplasm, arranged in tubulo-cystic, complex papillary, or solid architecture. OCCC arising from, or contiguous with, co-existent endometriosis or atypical endometrioid progenitors was also documented. For the purpose of this analysis, initial OCCC morphologic tissue descriptors were re-validated and curated with a quantitative OCCC immuno-histochemical (IHC) signature panel [[
Table 2 OCCC immuno-phenotypic characteristics according to Remmele and Stegner [[
Patient WT-1 ER p53 HNF1-ß* AMACR** NAPSIN-A ARID1A¶ 1 Moderate Negative Normal Moderate Negative Negative Positive 2 Negative Negative Normal Strong Moderate Weak Positive 3 Negative Negative Normal Strong Weak Negative Negative 4 Negative Negative Normal Strong Strong Moderate Positive 5 Negative Negative Normal Strong Moderate Negative Negative
*Hepatocyte nuclear factor-1ß ** Alpha methyl Acyl-CoA racemase AT-rich interaction domain 1A
The IHC stains were evaluated using the immuno-reactive Remmele score (IRS) [[
Acute and late (> 90 day) WART-related toxicity data was collected by physician and patient-reported assessments according to the Common Terminology Criteria for Adverse Events (CTCAE v4.03) [[
During WART, patients had weekly on-treatment clinical reviews which included history and physical examination and differential full blood count (FBC), and liver and kidney function tests. Post-WART oncologic reviews (history and physical examination, serum [CA-125], and hepato-renal biochemistry) were scheduled at week 6, week 12, and then quarterly for 2 years. Metabolic [FDG (18Fluoro-deoxyglucose) PET] re-staging was repeated on weeks 12, 52, and 104 (i.e. 2-year PET). From beginning of year 3, patients were seen 6-monthly, then annually after year-5. FDG-PET imaging was repeated if clinically indicated at any time.
Adjuvant WART commenced within 6 weeks of primary de-bulking surgery. An in-house automated dual iso-centre volumetrically modulated arc-based therapy (VMAT) technique was developed from the pre-clinical dosimetric modeling study of Mahantshetty et al. [[
For clarity in this analysis, we first curated the abdominal and pelvic WART planning target volumes (PTV) as low dose (PTV_Low) and high dose (PTV_High), respectively. Organ-at-risk (OAR) structure names (liver, lungs, heart, kidneys, bladder, and rectum) were also labeled according to the AAPM (American Association of Physicists in Medicine) Task Group 263 formalism [[
Patients were simulated and treated with an empty bladder. The patient was setup supine with arms-up using a combination Wing Board™ (Civco RT, Iowa) and pelvic BodyFix® cradle (Elekta AB, Sweden). A free-breathing planning 4-D CT was obtained without vascular contrast (except Patient 5) to capture full excursion of thoracic diaphragm and all intra-abdominal OAR motion. Patients were coached to replicate a smooth periodic respiratory motion. After CT acquisition, the entire parietal surface of the peritoneal cavity and including both thoracic and pelvic muscular diaphragms, was manually contoured as internal target volumes (ITV), expanded 5-10 mm, and subdivided into upper (or abdominal) low dose (PTV_Low) and lower (pelvic) high dose (PTV_High) planning target volumes. The level of the aortic bifurcation (Patients: 1–4) was chosen initially for this junction. Due to morbid obesity, Patient 5 had PTV_High confined to pelvic and distal para-aortic lymph nodes only (Fig. 1). Each PTV contained specific OAR structures which were separately contoured. The PTV_Low was expanded into the liver (10 mm) and kidney (5 mm) parenchyma as internal target margins to cover the peritoneal surface and account for any potential capsular infiltration. Validated normal tissue dose-volume tolerance parameters [[
Graph: Fig. 1 WART dose-volume distributions. Patients 1–4 (a) and Patient 5 (b). PTV_High (colored) confined to pelvis (a) and regional lymphatic compartment only (b). PTV_Low covers remainder of abdominal cavity
Table 3 Summary of WART dose volume analysis
Individual DVH parameters Group DVH parameters Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Min Max Median Mean PTV_High D 95% (Gy) 43.40 44.30 43.60 42.49 43.62 42.49 44.30 43.60 43.48 0.65 D 98% (Gy) 42.54 43.50 42.90 41.38 42.63 41.38 43.50 42.63 42.59 0.77 D 2% (Gy) 49.71 48.40 48.10 49.47 48.53 48.10 49.71 48.53 48.84 0.71 D 1% (Gy) 49.99 48.60 48.30 49.77 48.77 48.30 49.99 48.77 49.09 0.75 D 50% (Gy) 47.08 46.80 46.70 46.59 46.33 46.33 47.08 46.70 46.70 0.28 Max 51.23 49.76 49.35 51.69 50.40 49.35 51.69 50.40 50.49 0.98 Min 36.26 38.61 23.49 34.71 35.88 23.49 38.61 35.88 33.79 5.93 Mean 46.79 46.52 46.36 46.28 46.17 46.17 46.79 46.36 46.43 0.24 Length: craniocaudal (cm) 18.60 20.40 18.40 11.40 16.80 11.40 20.40 18.40 17.12 3.44 PTV_Low D 95% (Gy) 21.74 20.60 17.70 22.94 20.95 17.70 22.94 20.95 20.79 1.95 D 98% (Gy) 21.07 19.40 17.30 22.02 19.43 17.30 22.02 19.43 19.84 1.81 D 2% (Gy) 47.34 46.90 33.70 39.86 40.90 33.70 47.34 40.90 41.74 5.63 D 1% (Gy) 48.34 47.50 38.50 46.27 42.61 38.50 48.34 46.27 44.64 4.07 D 50% (Gy) 25.50 26.10 25.80 26.38 26.43 25.50 26.43 26.10 26.04 0.39 Max 50.21 49.13 48.07 51.38 50.27 48.07 51.38 50.21 49.81 1.26 Min 15.50 13.45 16.25 14.85 11.18 11.18 16.25 14.85 14.24 2.00 Mean 26.47 26.55 25.15 26.91 26.76 25.15 26.91 26.55 26.37 0.70 Length: craniocaudal (cm) 30.00 22.80 20.00 32.80 42.00 20.00 42.00 30.00 29.52 8.70 Kidneys V 20 Gy (%) 52.27 50.50 44.60 26.44 4.98 4.98 52.27 44.60 35.76 20.02 Mean 19.87 18.53 17.40 17.52 14.40 14.40 19.87 17.52 17.54 2.02 D 2% (Gy) 25.05 26.53 26.40 24.56 20.96 20.96 26.53 25.05 24.70 2.26 D 1% (Gy) 25.30 26.79 26.67 25.17 21.46 21.46 26.79 25.30 25.08 2.16 Kidney L V 20 Gy (%) 50.26 51.90 44.10 31.41 6.50 6.50 51.90 44.10 36.83 18.77 Mean 19.70 18.69 17.32 17.22 14.70 14.70 19.70 17.32 17.53 1.88 D 2% (Gy) 26.07 26.72 26.34 24.80 21.22 21.22 26.72 26.07 25.03 2.25 D 1% (Gy) 25.16 26.99 26.52 25.24 21.64 21.64 26.99 25.24 25.11 2.10 Kidney R 54.49 49.00 45.10 36.55 3.13 V 20 Gy (%) 19.99 18.37 17.50 18.94 14.16 3.13 54.49 45.10 37.65 20.38 Mean 25.01 26.26 26.50 25.80 20.43 14.16 19.99 18.37 17.79 2.22 D 2% (Gy) 25.30 26.48 27.69 26.22 21.04 20.43 26.50 25.80 24.80 2.51 D 1% (Gy) 21.04 27.69 26.22 25.35 2.55 Kidneys minus PTV V 20 Gy (%) 36.95 6.07 14.24 26.44 0.58 0.58 36.95 14.24 16.86 14.86 Mean 18.85 13.34 13.37 17.52 12.20 12.20 18.85 13.37 15.06 2.93 D 2% (Gy) 23.41 21.34 23.19 24.56 18.86 18.86 24.56 23.19 22.27 2.23 D 1% (Gy) 23.89 21.86 24.03 25.17 19.64 19.64 25.17 23.89 22.92 2.19 Bladder V 20 Gy (%) 100.00 100.00 100.00 100.00 99.00 99.00 100.00 100.00 99.80 0.45 V 40 Gy (%) 100.00 100.00 100.00 97.05 0.51 0.51 100.00 100.00 79.51 44.18 V 45 Gy (%) 98.24 99.00 99.70 92.83 0.00 0.00 99.70 98.24 77.95 43.66 Mean 47.43 47.32 46.73 47.00 27.18 27.18 47.43 47.00 43.13 8.92 D 2% (Gy) 49.22 48.79 47.76 49.58 35.99 35.99 49.58 48.79 46.27 5.79 D 1% (Gy) 49.36 48.94 47.87 49.79 38.30 38.30 49.79 48.94 46.85 4.83 Rectum V 20 Gy (%) 100.00 97.80 100.00 85.63 60.90 60.90 100.00 97.80 88.86 16.74 V 40 Gy (%) 95.49 79.90 98.30 70.18 17.84 17.84 98.30 79.90 72.34 32.57 V 45 Gy (%) 60.10 9.20 15.80 33.82 5.49 5.49 60.10 15.80 24.88 22.50 Mean 44.77 41.37 43.80 38.03 22.77 22.77 44.77 41.37 38.15 8.98 D 2% (Gy) 47.21 45.79 45.94 48.15 46.83 45.79 48.15 46.83 46.78 0.97 D 1% (Gy) 47.29 46.01 46.10 48.27 47.76 46.01 48.27 47.29 47.09 1.00 Liver V 20 Gy (%) 99.80 82.80 54.80 99.97 99.27 54.80 99.97 99.27 87.33 19.60 Mean 23.66 21.97 20.74 26.31 22.49 20.74 26.31 22.49 23.03 2.11 D 2% (Gy) 26.70 25.78 25.52 32.20 26.30 25.52 32.20 26.30 27.30 2.78 D 1% (Gy) 27.22 26.10 25.80 33.25 27.02 25.80 33.25 27.02 27.88 3.06 PTV_Total Length: craniocaudal (cm) 44.20 41.80 38.20 43.40 42.00 38.20 44.20 42.00 41.92 2.30 Isocentre Separation (cm) 15.00 10.00 14.00 20.00 15.00 10.00 20.00 15.00 14.80 3.56
PTV, planning target volume; D, dose; Gy, Gray; cm, centimetre; L, left; R, right; V, volume; Min, minimum; Max, maximum; SD, standard deviation
Prior to treatment, all WART dosimetric plans were quality validated with point-dose small volume ion chamber measurements in a multi-modality tissue equivalent phantom device (CIRS Inc, Virginia). In WART body regions representative of PTV_High and PTV_Low and, also within the junctional overlap region between the respective isocentres, a homogeneity pass criteria of ± 3% was accepted. Delivered photon fluence (photons per measured surface area) was assessed with the collimator jaws of the linear accelerator (TrueBeam®, Varian Medical Systems, Palo Alto) restricted to the active area of the mega-voltage (MV) diode panel. Portal Dosimetry prediction with a gamma pass criteria of 3 mm/3% was deemed acceptable. Fluence was also validated pre-clinically with photon delivery to a dual orthogonal plane diode array (Delta4 phantom, Scanditronix, Sweden). Pre-implementation modeling of uncertainties of cranio-caudal isocentre positioning (i.e. superior or inferior drift) did not significantly perturb the dose distribution within the total peritoneal target areas (PTV_Low + PTV_High) as the WART plans were optimized with combined superior and inferior fields together (i.e. not a base plan then additional isocentre fields added ex post facto). The positional separation of the isocentres (10-20 cm) was initially chosen to maximize the overlap (and dosimetric homogeneity) between the 25 Gy and 45 Gy target regions whilst maintaining sufficient cranio-caudal range to cover the long combined PTV (up to 45 cm).
Median age of the study group was 58 years (range 47–68 years) and most (3/5) had documented severe pre-morbid endometriosis requiring at least one exploratory or emergency laparotomy over a period ranging 25 or 30 years before OCCC diagnosis. Overall 3 women had early stage OCCC: FIGO (2018) Stage I (IC1, IA, and IC3). The latter case (IC3) had positive peritoneal cytology as did 2 others with more advanced disease, 1 with implant metastases to the fallopian tube (IIA), and another with both extra-pelvic peritoneal dissemination and small volume para-aortic lymph node metastasis (IIIA2). Median [CA-125] at presentation was 56 kU/L (range 18.4–370 kU/L) which normalized (< 38 kU/L) before WART in all cases (Table 1).
Table 2 summarizes the IHC phenotypic signature of the study group. Patient 1 was the only subject with bilateral OCCC; histomorphological features were identical between both tumors and typical for OCCC, though the immunoprofile showed moderate aberrant WT-1 staining and only weak HNF1-β. This was the oldest case, and the only case with a large volume of tumor necrosis. Both the age of the paraffin blocks and the poor baseline tumour viability may have contributed to its immunoprofile. The latter may also be supported by slight asymmetry seen in the immunostaining, with moderate HNF1-β intensity seen primarily on the side with the smaller, better preserved, less necrotic tumor.
Median post-WART follow-up was 77 months (range 16–83 mo.). All patients remain clinically, biochemically, and metabolically (
Intensity modulated WART was completed as a consecutive 5-week out-patient program without interruption in all patients. A multi-arc dual isocentre VMAT technique was deployed consisting of 2 superior arcs which treated the abdomen (PTV_Low) and 2 inferior arcs treated the pelvis (PTV_High). Cranio-caudally the iso-centres were separated by 10–20 cm (mean 14.8 cm ± 3.56 (SD) cm). This separation enabled an extended (combined PTV) treatment length (PTV_Low + PTV_High) of between 38.20 to 43.20 cm (mean 41.92 cm ± 2.3 cm). Automatic couch movement accuracy (± 2 mm) limited measured dosimetric inhomogeneity to less than 5% within the PTV junctional zone.
Evaluation parameters: A VMAT library of all 5 patients was created. Typical anatomical axial and coronal body dose wash and individual patient PTV dose-volume distributions and OAR exposures are depicted graphically in Fig. 2. Table 3 summarizes actual dose-volume-histogram (DVH) parameters for the PTVs and selected SOC-related OARs. Mean PTV_Low and PTV_High D95% coverage (dose to 95% of target volumes) were 20.9 Gy ± (SD) 2.0 Gy and 43.5 Gy (± 0.65 Gy), respectively. Mean liver and the combined kidney dose was 23 ± 19.6 Gy (SD) and 17.5 ± 2.0 Gy, respectively. Rectum (mean 38.2 ± 9 Gy) and bladder exposures (mean 43.1 ± 8.9 Gy) were dependent on inter-fractional (daily) filling with the respective organ volumes which received at least 45 Gy limited to 24.9% (± SD 22.5%) and 78% (± 43.7%). PTV_High in Patient 5 was personalized to include only the pelvic and para-aortic lymphatic compartments (Fig. 1).
Graph: Fig. 2 Individual and group DVH parameters
Common acute toxicities included low grade persistent nausea, diarrhea and cysto-urethritis which required symptomatic management (all CTCAE < G3) for approximately 2–6 weeks post-WART.
Figure 3 documents weekly fluctuations in mean hemoglobin concentration, total neutrophil and lymphocyte counts, and selected liver biochemistry during WART. There were no acute or post-week-12 perturbation in renal function (estimated GFR or serum creatinine; results not shown).
Graph: Fig. 3 Hemologic and hepatic parameters
At week 12 post-WART, 3 CTCAE (v4.03) system organ classes (SOC) were re-assessed on blood parameters A low grade lymphopenia (median lymphocyte count 0.7; range 0.6–1.2 × 10
One patient (Patient 3) developed a severe (CTCAE G3) late radiation injury to the gastrointestinal tract SOC. Emergent entero-colitis was detected at 9 months post-WART and required elective major small bowel and colon resection. This woman had previously suffered significant symptomatic endometriosis for 25 years and had had a prior adnexectomy for an ovarian torsion in addition to multiple open laparotomies for bowel obstruction and adhesions over this period. At last follow-up 71 months post-WART the patient was feeding orally but had combined supplemental enteral feeding (percutaneous endoscopic gastrostomy: PEG tube) and a permanent intravenous catheter for parenteral nutritional support. She has regained her pre-treatment performance status, musculo-skeletal composition (on DEXA-scan), body weight (55 kg), and has returned-to-work.
Ovarian clear cell cancer (OCCC) was first recognized as a distinct sub-type of epithelial ovarian cancer by the World Health Organization in 1973 [[
Within the major HNF-1 transcription network, HNF-1ß protein expression is almost ubiquitous in OCCC and uniquely characterizes its classical phenotype [[
We have demonstrated for the first time the clinical utility of adjuvant intensity-modulated whole abdominal radiation therapy (WART) in predominantly early stage optimally de-bulked OCCC with harmonious histo-morphic and phenotypic signatures which over-expressed HNF-1ß. At a median follow-up of 77 months, all treated women in our small cohort remain clinico-radiologically, and biochemically (CA-125) cancer-free with good self-reported quality of life.
Late gastro-intestinal toxicity remains the dominant serious emergent hazard of WART [[
Two patients were detected with asymptomatic (CTCAE G2) fractures of the sacrum and lumbar vertebra on planned FDG-PET surveillance at 1-year. Osteoporotic fragility fractures are probably under-reported in post-menopausal women following pelvic and extended pelvic irradiation for gynecologic cancer [[
Adjuvant WART for epithelial ovarian cancer is not new. Developed in North America and Canada in the pre-platinum era (1960–1985), WART was once a transformative treatment with real strategic intent for the management of ovarian cancer [[
Historical WART techniques consisted of large anterior and posterior radiation portals as either "opposed open-field" (or classic PMH technique [[
Despite the short-comings, WART has improved long-term progression-free and overall survival in optimally de-bulked Stage I-III ovarian cancer patients [[
The strengths and limitations of pragmatic observational studies to inform clinical decision making have been recently outlined in a research statement by the American Society of Clinical Oncology [[
The internal validity of our study was further strengthened by the treatment of a histologically harmonious cohort of OCCC patients with full adherence to a conceptually uniform WART protocol, and standardized follow-up assessments. Our WART database was enhanced by curation of radiation target volumes and critical avoidance organs to the AAPM Task Group 263 nomenclature [[
In conclusion, we believe intensity modulated WART has excellent clinical utility in optimally de-bulked women with histologically confirmed pure OCCC whose phenotypic signature includes HNF-1β over-expression. Rigorous future observational research malleable to "Big Data" collaboration is needed to enhance the evidence-base supporting this imminently actionable radiation technique.
MS, SW, and GG study conceptualization. MS, CR, DN, AL data curation. MS formal analysis. SW investigations. MS, SW, GG, SR study methodology. Original draft of manuscript MS, SW, GG. Review and editing of manuscript MS, SW, GG, CR, DN, SR, AL. All authors read and approved the final manuscript.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
This study was pre-approved by the Northern Sydney Local Health District (NSLHD) and included patients who had consented to the use of their oncologic and general medical data stored by the Northern Sydney Cancer Center for clinical follow-up and research purposes.
Not applicable.
The authors declare that they have no competing interests.
• AAPM
- American Association of Physics in Medicine
• AMACR
- Alpha methyl Acyl-CoA racemase
• ARID1A
- AT-rich interaction domain 1A
• CT
- Computed tomography
• CTCAE
- Common terminology criteria for adverse events
- ER-α
- Estrogen receptor-alpha
• FBC
- Full blood count
-
18 FDG-PET -
18 Fluoro-deoxyglucose positron emission tomography
• FIGO
- Federation of gynecology and obstetrics
• HNF
- Hepatocyte nuclear factor
• HRR
- Homologous recombination repair
• IARC
- International Agency for Research on Cancer
• IHC
- Immuno-histochemical
• ITV
- Internal target volumes
• NER
- Nucleotide excision repair
• NSLHD
- Northern Sydney Local Health District
• OAR
- Organ at risk
• OCCC
- Ovarian clear cell cancer
• PTV
- Planning target volume
- PTV_High
- Planning target volume high dose
- PTV_Low
- Planning target volume low dose
• SOC
- System organ classes
• VMAT
- Volumetric modulated arc therapy
• WART
- Whole abdominal radiation therapy
• WT-1
- Wilm's tumor suppressor
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By Mark J. Stevens; Simon West; Gregory Gard; Christopher Renaud; David Nevell; Stephanie Roderick and Andrew Le
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