Radiation Oncology - Latest Articles

18F-FDG PET/CT-based gross tumor volume definition for radiotherapy in head and neck Cancer: a correlation study between suitable uptake value threshold and tumor parameters

Chia-Hung Kao — 2010-09-02T00:00:00Z

Background: To define a suitable threshold setting for gross tumor volume (GTV) when using 18Fluoro-deoxyglucose positron emission tomography and computed tomogram (PET/CT) for radiotherapy planning in head and neck cancer (HNC). Methods: Fifteen HNC patients prospectively received PET/CT simulation for their radiation treatment planning. Biological target volume (BTV) was derived from PET/CT-based GTV of the primary tumor. The BTVs were defined as the isodensity volumes when adjusting different percentage of the maximal standardized uptake value (SUVmax), excluding any artifact from surrounding normal tissues. CT-based primary GTV (C-pGTV) that had been previously defined by radiation oncologists was compared with the BTV. Suitable threshold level (sTL) could be determined when BTV value and its morphology using a certain threshold level was observed to be the best fitness of the C-pGTV. Suitable standardized uptake value (sSUV) was calculated as the sTL multiplied by the SUVmax.Result: Our result demonstrated no single sTL or sSUV method could achieve an optimized volumetric match with the C-pGTV. The sTL was 13% to 27% (mean, 19%), whereas the sSUV was 1.64 to 3.98 (mean, 2.46). The sTL was inversely correlated with the SUVmax [sTL = -0.1004 Ln (SUVmax) + 0.4464; R2 = 0.81]. The sSUV showed a linear correlation with the SUVmax (sSUV = 0.0842 SUVmax + 1.248; R2 = 0.89). The sTL was not associated with the value of C-pGTVs. Conclusion: In PET/CT-based BTV for HNC, a suitable threshold or SUV level can be established by correlating with SUVmax rather than using a fixed threshold.

The role of adjuvant pelvic radiotherapy in rectal cancer with synchronous liver metastasis: a retrospective study

Jun Won Kim — 2010-08-31T00:00:00Z

Background: Synchronous liver metastases are detected in approximately 25% of colorectal cancer patients at diagnosis. The rates of local failure and distant metastasis are substantial in these patients, even after undergoing aggressive treatments including resection of primary and metastatic liver tumors. The purpose of this study was to determine whether adjuvant pelvic radiotherapy is beneficial for pelvic control and overall survival in rectal cancer patients with synchronous liver metastasis after primary tumor resection. Methods: Among rectal cancer patients who received total mesorectal excision (TME) between 1997 and 2006 at Yonsei University Health System, eighty-nine patients diagnosed with synchronous liver metastasis were reviewed. Twenty-seven patients received adjuvant pelvic RT (group S + R), and sixty-two patients were managed without RT (group S). Thirty-six patients (58%) in group S and twenty patients (74%) in group S+R received local treatment for liver metastasis. Failure patterns and survival outcomes were analyzed. Results: Pelvic failure was observed in twenty-five patients; twenty-one patients in group S (34%), and four patients in group S+R (15%) (p = 0.066). The two-year pelvic failure-free survival rates (PFFS) of group S and group S+R were 64.8% and 80.8% (p = 0.028), respectively, and the two-year overall survival rates (OS) were 49.1% and 70.4% (p = 0.116), respectively. In a subgroup analysis of fifty-six patients who received local treatment for liver metastasis, the two-year PFFS were 64.9% and 82.9% (p = 0.05), respectively; the two-year OS were 74.1% and 80.0% (p = 0.616) in group S (n = 36) and group S+R (n = 20), respectively. Conclusions: Adjuvant pelvic RT significantly reduced the pelvic failure rate but its influence on overall survival was unclear. Rectal cancer patients with synchronous liver metastasis may benefit from adjuvant pelvic RT through an increased pelvic control rate and improved quality of life.

An investigation of intensity-modulated radiation therapy versus conventional two-dimensional and 3D-conformal radiation therapy for early stage larynx cancer

Daniel Gomez — 2010-08-26T00:00:00Z

IntroductionIntensity modulated radiation therapy (IMRT) has been incorporated at several institutions for early stage laryngeal cancer (T1/T2N0M0), but its utility is controversial. Methods: In three representative patients, multiple plans were generated: 1) Conventional 2D planning, with the posterior border placed at either the anterior aspect ("tight" plan) or the mid-vertebral body ("loose" plan), 2) 3D planning, utilizing both 1.0 and 0.5 cm margins for the planning target volume (PTV), and 3) IMRT planning, utilizing the same margins as the 3D plans. A dosimetric comparison was performed for the target volume, spinal cord, arytenoids, and carotid arteries. The prescription dose was 6300 cGy (225 cGy fractions), and the 3D and IMRT plans were normalized to this dose. Results: For PTV margins of 1.0 cm and 0.5 cm, the D95 of the 2D tight/loose plans were 3781/5437 cGy and 5372/5869 cGy, respectively (IMRT/3D plans both 6300 cGy). With a PTV margin of 1.0 cm, the mean carotid artery dose was 2483/5671/5777/4049 cGy in the 2D tight, 2D loose, 3D, and IMRT plans, respectively. When the PTV was reduced to 0.5 cm, the the mean carotid artery dose was 2483/5671/6466/2577 cGy to the above four plans, respectively. The arytenoid doses were similar between the four plans, and spinal cord doses were well below tolerance. Conclusions: IMRT provides a more ideal dose distribution compared to 2D treatment and 3D planning in regards to mean carotid dose. We therefore recommend IMRT in select cases when the treating physician is confident with the GTV.

Prospective evaluation of microscopic extension using whole-mount preparation in patients with hepatocellular carcinoma: Definition of clinical target volume for radiotherapy

Weihu Wang — 2010-08-23T00:00:00Z

Backgroud: To define the clinical target volume (CTV) for radiotherapy in patients with hepatocellular carcinoma (HCC). Methods: A prospective study was conducted to histologically evaluate the presence and the distance of microscopic extension (ME) for resected HCC on the basis of examination of whole-mount preparations of carcinoma tissue sections. Results: A total of 380 whole-mount slides prepared from tumor samples of 76 patients with HCC were examined. Patients with elevated pretreatment AFP levels exhibited higher risk of ME as compared to those with normal pretreatment AFP levels (93.9% vs. 69.8%, P<0.01). ME positivity was 16.7% for Grade 1, 79.1% for Grade 2, and 96.3% for Grade 3 tumors (P<0.01). The mean distance of ME was 0.0+/-0.1 mm ( range 0-0.2 mm) for Grade 1, 0.9+/-0.9 mm (range 0-4.5 mm) for Grade 2, and 1.9+/-1.9 mm (range 0-8.0 mm) for Grade 3 tumors (P<0.01). Conclusions: The CTV margins for tumor Grades 1, 2, and 3 HCC, are recommended to be 0.2 mm, 4.5 mm, and 8.0 mm beyond the gross tumor margin, respectively, to account for possible ME of the tumors in all patients.

Validation of bidimensional measurement in nasopharyngeal carcinoma

Ting-Shou Chang — 2010-08-16T00:00:00Z

Background: Our previous study showed a close relationship between computed tomography (CT)-derived bidimensional measurement of primary tumor and retropharyngeal nodes (BDMprn) and gross tumor volume of primary tumor and retropharyngeal nodes (GTVprn) in nasopharyngeal carcinoma (NPC) and better prognosis for NPC patients with smaller BDMprn. In this study, we report the results on of a study to validate the use of BDM in a separate cohort of NPC patients. Methods: We retrospectively reviewed 103 newly diagnosed NPC cases who were treated with radiotherapy/concurrent chemoradiotherapy (CCRT) or CCRT with adjuvant chemotherapy from 2002 to 2009. We used magnetic resonance imaging (MRI) to measure BDMprn. We calculated overall survival, recurrence-free and distant metastasis-free survival curves and set a BDMprn cut off point to categorize patients into a high- or low-risk group. We then used Cox proportional hazard model to evaluate the prognostic influence of BDMprn after correcting age, gender and chemotherapy status. Results: After adjusting for age, gender, and chemotherapy status, BDMprn remained an independent prognostic factor for distant metastasis [Hazard ratio (HR) = 1.046; P = 0.042] and overall survival (HR = 1.012; P = 0.012). Patients with BDMprn < 15 cm2 had a greater 3-year overall survival rate than those with BDMprn ≧ 15 cm2 (92.3% vs. 73.7%; P = 0.009). They also had a greater 3-year distant metastasis-free survival (94% vs.75%; P = 0.034). Conclusion: The predictive ability of BDMprn was validated in a separate NPC cohort. A BDMprn of 15 cm2 can be used to separate NPC patients into high- and low-risk groups and predict survival rates and metastasis potential. It can, therefore, be used as a reference to design clinical trials, predict prognosis, and make treatment decisions.

Tumor response to radiotherapy is dependent on genotype-associated mechanisms In vitro and in vivo.

Jerry Williams — 2010-08-12T00:00:00Z

Background: We have previously shown that in vitro radiosensitivity of human tumor cells segregate non-randomly into a limited number of groups. Each group associates with a specific genotype. However we have also shown that abrogation of a single gene (p21) in a human tumor cell unexpectedly sensitized xenograft tumors comprised of these cells to radiotherapy while not affecting in vitro cellular radiosensitivity. Therefore in vitro assays alone cannot predict tumor response to radiotherapy.In the current work, we measure in vitro radiosensitivity and in vivo response of their xenograft tumors in a series of human tumor lines that represent the range of radiosensitivity observed in human tumor cells. We also measure response of their xenograft tumors to different radiotherapy protocols. We reduce these data into a simple analytical structure that defines the relationship between tumor response and total dose based on two coefficients that are specific to tumor cell genotype, fraction size and total dose. Methods: We assayed in vitro survival patterns in eight tumor cell lines that vary in cellular radiosensitivity and genotype. We also measured response of their xenograft tumors to four radiotherapy protocols: 8 × 2 Gy; 2 × 5Gy, 1 × 7.5 Gy and 1 × 15 Gy. We analyze these data to derive coefficients that describe both in vitro and in vivo responses. Results: Response of xenografts comprised of human tumor cells to different radiotherapy protocols can be reduced to only two coefficients that represent 1) total cells killed as measured in vitro 2) additional response in vivo not predicted by cell killing. These coefficients segregate with specific genotypes including those most frequently observed in human tumors in the clinic. Coefficients that describe in vitro and in vivo mechanisms can predict tumor response to any radiation protocol based on tumor cell genotype, fraction-size and total dose. Conclusions: We establish an analytical structure that predicts tumor response to radiotherapy based on coefficients that represent in vitro and in vivo responses. Both coefficients are dependent on tumor cell genotype and fraction-size. We identify a novel previously unreported mechanism that sensitizes tumors in vivo; this sensitization varies with tumor cell genotype and fraction size.

Radiosensitization and growth inhibition of cancer cells mediated by an scFv antibody gene against DNA-PKcs in vitro and in vivo

Li Du — 2010-08-12T00:00:00Z

Background: Overexpression of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is commonly occurred in cancers and causes radioresistance and poor prognosis. In present study, the single-chain variable antibody fragments (scFv) targeting DNA-PKcs was developed for the application of radiosensitization in vitro and in vivo. A humanized semisynthetic scFv library and the phage-display antibodies technology were employed to screen DNA-PKcs scFv antibody. Methods: DNA-PKcs epitopes were predicted and cloned. A humanized semisynthetic scFv library and the phage-display antibodies technology were employed to screen DNA-PKcs scFv antibody. DNA damage repair was analyzed by comet assay and immunofluorescence detection of γH2AX foci. The radiosensitization in vivo was determined on Balb/c athymic mice transplanted tumours of HeLa cells. Results: Four epitopes of DNA-PKcs have been predicted and expressed as the antigens, and a specific human anti-DNA-PKcs scFv antibody gene, anti-DPK3-scFv, was obtained by screening the phage antibody library using the DNA-PKcs peptide DPK3. The specificity of anti-DPK3-scFv was verified, in vitro. Transfection of HeLa cells with the anti-DPK3-scFv gene resulted in an increased sensitivity to IR, decreased repair capability of DNA double-strand breaks (DSB) detected by comet assay and immunofluorescence detection of γH2AX foci. Moreover, the kinase activity of DNA-PKcs was inhibited by anti-DPK3-scFv, which was displayed by the decreased phosphorylation levels of its target Akt/S473 and the autophosphorylation of DNA-PKcs on S2056 induced by radiation. Measurement of the growth and apoptosis rates showed that anti-DPK3-scFv enhanced the sensitivity of tumours transplanted in Balb/c athymic mice to radiation therapy. Conclusion: The antiproliferation and radiosensitizing effects of anti-DPK3-scFv via targeting DNA-PKcs make it very appealing for the development as a novel biological radiosensitizer for cancer therapeutic potential.

The effect of external beam radiotherapy volume on locoregional control in patients with locoregionally advanced or recurrent nonanaplastic thyroid cancer

Tae Hyun Kim — 2010-08-06T00:00:00Z

PurposeWe evaluated outcomes of patients treated with external beam radiotherapy (EBRT) for locoregionally advanced or recurrent nonanaplastic thyroid cancer and analyzed the effect of EBRT volume on locoregional control. Methods: This study included 23 patients with locoregionally advanced or recurrent nonanaplastic thyroid cancer who were treated with EBRT. Two different EBRT target volumes were executed as follows: 1) limited field (LF, n = 11) included the primary (involved lobe) or recurrent tumor bed and the positive nodal area; 2) elective field (EF, n = 12) included the primary (involved lobe) or recurrent tumor bed and the regional nodal areas in the cervical neck and upper mediastinum. Clinical parameters, such as gender, age, histologic type, recurrence, stage, thyroglobulin level, postoperative residuum, radioiodine treatment, and EBRT volume were analyzed to identify prognostic factors associated with locoregional control. Results: There were no significant differences in the clinical parameter distributions between the LF and EF groups. In the LF group, six (55%) patients developed locoregional recurrence and three (27%) developed distant metastasis. In the EF group, one (8%) patient developed locoregional recurrence and one (8%) developed a distant metastasis. There was a significant difference in locoregional control rate at 5 years in the LF and EF groups (40% vs. 89%, p = 0.041). There were no significant differences in incidences of acute and late toxicities between two groups (p > 0.05). Conclusions: EBRT with EF provided significantly better locoregional control than that of LF; however, further larger scaled studies are warranted.

CT-guided iodine-125 seed permanent implantation for recurrent head and neck cancers

Yu Jiang — 2010-07-30T00:00:00Z

Background: To investigate the feasibility, and safety of 125I seed permanent implantation for recurrent head and neck carcinoma under CT-guidance. Results: A retrospective study on 14 patients with recurrent head and neck cancers undergone 125I seed implantation with different seed activities. The post-plan showed that the actuarial D90 of 125I seeds ranged from 90 to 218 Gy (median, 157.5 Gy). The follow-up was 3 to 60 months (median, 13 months). The median local control was 18 months (95% CI, 6.1-29.9 months), and the 1-, 2-, 3-, and 5- year local controls were 52%, 39%, 39%, and 39%, respectively. The 1-, 2-, 3-, and 5- survival rates were 65%, 39%, 39% and 39%, respectively, with a median survival time of 20 months (95% CI, 8.7-31.3 months). Of all patients, 28.6% (4/14) died of local recurrence, 7.1% (1/14) died of metastases, one patient died of hepatocirrhosis, and 8 patients are still alive to the date of data analysis. Conclusion: CT-guided 125I seed implantation is feasible and safe as a salvage or palliative treatment for patients with recurrent head and neck cancers.

Prospective multi-center trial utilizing electronic brachytherapy for the treatment of endometrial cancer

Adam Dickler — 2010-07-20T00:00:00Z

Background: A modified form of high dose rate (HDR) brachytherapy has been developed called Axxent Electronic Brachytherapy (EBT). EBT uses a kilovolt X-ray source and does not require treatment in a shielded vault or a HDR afterloader unit. A multi-center clinical study was carried out to evaluate the success of treatment delivery, safety and toxicity of EBT in patients with endometrial cancer. Methods: A total of 15 patients with stage I or II endometrial cancer were enrolled at 5 sites. Patients were treated with vaginal EBT alone or in combination with external beam radiation. Results: The prescribed doses of EBT were successfully delivered in all 15 patients. From the first fraction through 3 months follow-up, there were 4 CTC Grade 1 adverse events and 2 CTC Grade II adverse events reported that were EBT related. The mild events reported were dysuria, vaginal dryness, mucosal atrophy, and rectal bleeding. The moderate treatment related adverse events included dysuria, and vaginal pain. No Grade III or IV adverse events were reported. The EBT system performed well and was associated with limited acute toxicities. Conclusions: EBT shows acute results similar to HDR brachytherapy. Additional research is needed to further assess the clinical efficacy and safety of EBT in the treatment of endometrial cancer.