Comparison of initial and sequential salvage brain-directed treatment in patients with 1-4 vs. 5-10 brain metastases from breast cancer (KROG 16-12).

PURPOSE: We aimed to compare the initial and salvage brain-directed treatment and overall survival (OS) between patients with 1-4 brain metastases (BMs) and those with 5-10 from breast cancer (BC). We also organized a decision tree to select the initial whole-brain radiotherapy (WBRT) for these patients. METHODS: Between 2008 and 2014, 471 patients were diagnosed with 1-10 BMs. They were divided into two groups based on the number of BM: 1-4 BMs (n = 337) and 5-10 BMs (n = 134). Median follow-up duration was 14.0 months. RESULTS: Stereotactic radiosurgery (SRS)/fractionated stereotactic radiotherapy (FSRT) was the most common treatment modality (n = 120, 36%) in the 1-4 BMs group. In contrast, 80% (n = 107) of patients with 5-10 BMs were treated with WBRT. The median OS of the entire cohort, 1-4 BMs, and 5-10 BMs was 18.0, 20.9, and 13.9 months, respectively. In the multivariate analysis, the number of BM and WBRT were not associated with OS, whereas triple-negative BC and extracranial metastasis decreased OS. Physicians determined the initial WBRT based on four variables in the following order: number and location of BM, primary tumor control, and performance status. Salvage brain-directed treatment (n = 184), mainly SRS/FSRT (n = 109, 59%), prolonged OS by a median of 14.3 months. CONCLUSION: The initial brain-directed treatment differed notably according to the number of BM, which was chosen based on four clinical factors. In patients with ≤ 10 BMs, the number of BM and WBRT did not affect OS. The major salvage brain-directed treatment modality was SRS/FSRT and increased OS.

Comparison of treatment outcomes of pelvis external radiotherapy with and without vaginal brachytherapy for cervical cancer patients with positive or close vaginal resected margins.

BACKGROUND: We evaluated whether there is a difference in the local recurrence and survival after pelvic external radiotherapy (ERT) with and without boost vaginal brachytherapy (VB) in cervical cancer patients with positive or close vaginal resected margins (RM). METHODS: We retrospectively reviewed FIGO stage IA-IIB cervical cancer patients treated with postoperative ERT between 1997 and 2018. The sixty patients showing close (safety margin < 5 mm) or positive vaginal RM were included. ERT was delivered with median 50.4 Gy in 28 fractions to the pelvis and VB with median 30 Gy in 6 fractions. RESULTS: The median follow-up duration was 46 months. Five out of 30 patients treated with ERT alone experienced vaginal recurrence within 2 years after surgery. The 5-year local control (LC) was 100% in patients receiving ERT + VB compared with 81.3% in patients receiving ERT alone (log rank p = 0.022). The 5-year pelvic control (PC) was 95.8% for patients receiving ERT + VB and 76.8% for ERT alone (p = 0.041). The 5-year overall survival and recurrence-free survival (RFS) were not significantly different between treatment groups. In multivariate analysis, perineural invasion was a significant risk factor for PC (p = 0.024). Parametrial involvement (p = 0.044) and vascular invasion (p = 0.032) were unfavorable prognostic factors for RFS. Late toxicity occurrences were not significant in both groups. CONCLUSION: VB after ERT improved LC and PC in cervical cancer patients with close or positive RM after hysterectomy. The toxicities were not increased after VB was added to ERT.

Mebendazole Increases Anticancer Activity of Radiotherapy in Radiotherapy-Resistant Triple-Negative Breast Cancer Cells by Enhancing Natural Killer Cell-Mediated Cytotoxicity.

Breast cancer is the most commonly diagnosed cancer worldwide and ranks first in terms of both prevalence and cancer-related mortality in women. In this study, we aimed to evaluate the anticancer effect of mebendazole (MBZ) and radiotherapy (RT) concomitant use in triple-negative breast cancer (TNBC) cells and elucidate the underlying mechanisms of action. Breast cancer mouse models and several types of breast cancer cells, including TNBC-derived RT-resistant (RT-R) MDA-MB-231 cells, were treated with MBZ and/or RT. In mice, changes in body weight, renal and liver toxicity, tumor volume, and number of lung metastases were determined. In cells, cell viability, colony formation, scratch wound healing, Matrigel invasion, and protein expression using western blotting were determined. Our findings showed that MBZ and RT combined treatment increased the anticancer effect of RT without additional toxicity. In addition, we noted that cyclin B1, PH2AX, and natural killer (NK) cell-mediated cytotoxicity increased following MBZ + RT treatment compared to unaided RT. Our results suggest that MBZ + RT have an enhanced anticancer effect in TNBC which acquires radiation resistance through blocking cell cycle progression, initiating DNA double-strand breaks, and promoting NK cell-mediated cytotoxicity.

New brain metastases after whole-brain radiotherapy of initial brain metastases in breast cancer patients: the significance of molecular subtypes (KROG 16-12).

PURPOSE: To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). METHODS: In this multi-institutional study, 538 BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-, n = 136), HER2-positive (HER2+, n = 253), or triple-negative BC (TNBC, n = 149). RESULTS: In 37.4% of patients, new BM emerged at a median of 10.5 months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2-, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively (p = 0.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1 year, p < 0.001) according to molecular subtype (HR+/HER2-, 42% reduction at 1 year, p < 0.001; HER2+, 18.5%, p = 0.004; TNBC, 16.9%, p = 0.071). Multivariate analysis revealed an increased risk of new BM for the following factors: shorter intervals between primary BC diagnoses and BM (p = 0.031); TNBC (relative to HR+/HER2-) (p = 0.016); presence of extracranial metastases (p = 0.019); number of BM (>4) (p < 0.001); and BM in both tentorial regions (p = 0.045). Anti-HER2 therapy in HER2+ patients (p = 0.013) and initial use of WBRT (p < 0.001) significantly lowered new BM development. CONCLUSIONS: Tumor molecular subtypes were associated with both rates of new BM development and the effectiveness of initial WBRT. Anti-HER2 therapy in HER2+ patients significantly lowered new BM occurrence.

Abscopal Effect of Radiotherapy Enhanced with Immune Checkpoint Inhibitors of Triple Negative Breast Cancer in 4T1 Mammary Carcinoma Model.

Local radiotherapy (RT) is important to manage metastatic triple-negative breast cancer (TNBC). Although RT primarily reduces cancer cells locally, this control can be enhanced by triggering the immune system via immunotherapy. RT and immunotherapy may lead to an improved systemic effect, known as the abscopal effect. Here, we analyzed the antitumor effect of combination therapy using RT with an anti-programmed cell death-1 (PD-1) antibody in primary tumors, using poorly immunogenic metastatic mouse mammary carcinoma 4T1 model. Mice were injected subcutaneously into both flanks with 4T1 cells, and treatment was initiated 12 days later. Mice were randomly assigned to three treatment groups: (1) control (no treatment with RT or immune checkpoint inhibitor (ICI)), (2) RT alone, and (3) RT+ICI. The same RT dose was prescribed in both RT-alone and RT+ICI groups as 10Gy/fx in two fractions and delivered to only one of the two tumor burdens injected at both sides of flanks. In the RT+ICI group, 200 µg fixed dose of PD-1 antibody was intraperitoneally administered concurrently with RT. The RT and ICI combination markedly reduced tumor cell growth not only in the irradiated site but also in non-irradiated sites, a typical characteristic of the abscopal effect. This was observed only in radiation-sensitive cancer cells. Lung metastasis development was lower in RT-irradiated groups (RT-only and RT+ICI groups) than in the non-irradiated group, regardless of the radiation sensitivity of tumor cells. However, there was no additive effect of ICI on RT to control lung metastasis, as was already known regarding the abscopal effect. The combination of local RT with anti-PD-1 blockade could be a promising treatment strategy against metastatic TNBC. Further research is required to integrate our results into a clinical setting.

Anticancer Effect of Benzimidazole Derivatives, Especially Mebendazole, on Triple-Negative Breast Cancer (TNBC) and Radiotherapy-Resistant TNBC In Vivo and In Vitro.

In this study, we aimed to evaluate the anticancer effect of benzimidazole derivatives on triple-negative breast cancer (TNBC) and investigate its underlying mechanism of action. Several types of cancer and normal breast cells including MDA-MB-231, radiotherapy-resistant (RT-R) MDA-MB-231, and allograft mice were treated with six benzimidazole derivatives including mebendazole (MBZ). Cells were analyzed for viability, colony formation, scratch wound healing, Matrigel invasion, cell cycle, tubulin polymerization, and protein expression by using Western blotting. In mice, liver and kidney toxicity, changes in body weight and tumor volume, and incidence of lung metastasis were analyzed. Our study showed that MBZ significantly induced DNA damage, cell cycle arrest, and downregulation of cancer stem cell markers CD44 and OCT3/4, and cancer progression-related ESM-1 protein expression in TNBC and RT-R-TNBC cells. In conclusion, MBZ has the potential to be an effective anticancer agent that can overcome treatment resistance in TNBC.

Alpha-Lipoic Acid Ameliorates Radiation-Induced Salivary Gland Injury by Preserving Parasympathetic Innervation in Rats.

Radiation therapy is a standard treatment for patients with head and neck cancer. However, radiation exposure to the head and neck induces salivary gland (SG) dysfunction. Alpha lipoic acid (ALA) has been reported to reduce radiation-induced toxicity in normal tissues. In this study, we investigated the effect of ALA on radiation-induced SG dysfunction. Male Sprague-Dawley rats were assigned to the following treatment groups: control, ALA only (100 mg/kg, intraperitoneally), irradiation only, and ALA administration 24 h or 30 min prior to irradiation. The neck area, including SGs, was irradiated evenly at 2 Gy/min (total dose, 18 Gy) using a photon 6 MV linear accelerator. The rats were sacrificed at 2, 6, 8, and 12 weeks after irradiation. Radiation decreased SG weight, saliva secretion, AQP5 expression, parasympathetic innervation (GFRα2 and AchE expression), regeneration potentials (Shh and Ptch expression), salivary trophic factor levels (brain-derived neurotrophic factor and neurturin), and stem cell expression (Sca-1). These features were restored by treatment with ALA. This study demonstrated that ALA can rescue radiation-induced hyposalivation by preserving parasympathetic innervation and regenerative potentials.

Who Really Benefits from 3D-Based Planning of Brachytherapy for Cervical Cancer?

BACKGROUND: Although intracavitary radiotherapy (ICR) is essential for the radiation therapy of cervical cancer, few institutions in Korea perform 3-dimensional (3D)-based ICR. To identify patients who would benefit from 3D-based ICR, dosimetric parameters for tumor targets and organs at risk (OARs) were compared between 2-dimensional (2D)- and 3D-based ICR. METHODS: Twenty patients with locally advanced cervical cancer who underwent external beam radiation therapy (EBRT) following 3D-based ICR were retrospectively evaluated. New 2D-based plans based on the Manchester system were developed. Tumor size was measured by magnetic resonance imaging. RESULTS: The mean high risk clinical target volume (HR-CTV) D90 value was about 10% lower for 2D- than for 3D-based plans (88.4% vs. 97.7%; P = 0.068). Tumor coverage did not differ between 2D- and 3D-based plans in patients with tumors ≤ 4 cm at the time of brachytherapy, but the mean HR-CTV D90 values in patients with tumors > 4 cm were significantly higher for 3D-based plans than for 2D-based plans (96.0% vs. 78.1%; P = 0.017). Similar results were found for patients with tumors > 5 cm initially. Other dosimetric parameters for OARs were similar between 2D- and 3D-based plans, except that mean sigmoid D2cc was higher for 2D- than for 3D-based plans (67.5% vs. 58.8%; P = 0.043). CONCLUSION: These findings indicate that 3D-based ICR plans improve tumor coverage while satisfying the dose constraints for OARs. 3D-based ICR should be considered in patients with tumors > 4 cm size at the time of brachytherapy or > 5 cm initially.

Analysis of Motion-dependent Clinical Outcome of Tumor Tracking Stereotactic Body Radiotherapy for Prostate Cancer.

BACKGROUND: To analyze clinical outcome of CyberKnife (CK) tumor-tracking stereotactic body radiotherapy (SBRT) for prostate cancer (Pca) according to the magnitude of intra-fractional prostate motion. METHODS: Medical records and daily treatment logs for 71 patients who received CK tumor-tracking SBRT were retrospectively analyzed. Statistical relationships between prostate motion and various outcome results, including local recurrence (LR), biochemical failure (BF), and treatment-related toxicity, were investigated in order to evaluate motion-dependent efficacy of tumor-tracking SBRT for Pca. RESULTS: In a total 71 patients, 3 (4.2%) patients with LR, 12 (16.9%) patients with BF, and 22 (31%) patients with grade-II or worse toxicities to rectal or bladder (22 to rectal, 22 to bladder and 8 patients to both) were observed in a median follow-up of 47 months. Magnitudes of intra-fractional tumor motion along superior-inferior, right-left, and anterior-posterior (AP) axes were 0.15 ± 0.31, 0.12 ± 0.19, and 0.73 ± 0.32 mm, respectively. Radial magnitude was estimated to be 1.0 ± 0.35 mm. Intra-fractional movement was not significantly correlated with tumor control. However, it was significant correlated with the incidence of grade-II or worse toxicity to rectum or bladder particularly when tumor motion was in the AP axis. CONCLUSION: Our quantitative results revealed that toxicity related to SBRT treatment was highly sensitive to intra-fractional prostate movements, although local-tumor control was not affected by such movements. Our results demonstrate that precise motion correction is essential in prostate SBRT, even if it seems to be small.

Role of radiation therapy in primary central nervous system lymphoma : KROG 14-20 Collaborative Study of Brain and Lymphoma Committee.

We analyzed patterns of care and outcomes for patients with primary central nervous system lymphoma (PCNSL) in this multi-institutional retrospective study. Between January 2000 and December 2011, 220 patients with PCNSL received radiotherapy (RT). Among these patients, 26 patients received RT alone; 179 patients were treated with chemotherapy and radiotherapy; the rest of the patients (N = 15) initially underwent chemotherapy alone, then received RT as a salvage treatment. Most of the patients (N = 188) received methotrexate-based chemotherapy. The median follow up duration was 38 months (range 3-179 months). The median RT dose and whole brain RT (WBRT) dose were 45.0 Gy (range 20.0-59.4) and 30.6 Gy (range 18.0-45.0), respectively. Seventy-seven (35%) patients received WBRT alone, and 143 patients (65%) underwent WBRT plus boost RT. Total RT dose and WBRT dose decreased during the study period. The median survival was 64 months and actuarial 5-year overall survival was 51.4%. In multivariate analysis, age (P < 0.001), ECOG performance status (P = 0.036), deep structure involvement (P = 0.011) and treatment response (P = 0.001) were significant prognosticators. RT combined with chemotherapy is effective modality for treatment of PCNSL. The survival outcome improved in spite of total radiation dose and whole brain RT (WBRT) dose having been decreased over the study period, indicating that low-dose WBRT could be effective.

Wait and see approach for rectal cancer with a clinically complete response after neoadjuvant concurrent chemoradiotherapy.

PURPOSE: Rectal cancer patients with a pathological complete response (pCR) after neoadjuvant concurrent chemoradiotherapy (CCRT) have a better prognosis compared to those without a pCR. Therefore, the "Wait and See" (W&S) approach in those who achieved clinically complete response (cCR) after CCRT was introduced as an alternative modality to the total mesorectal excision (TME). The aim of this study was to compare the oncological outcomes between W&S and TME via meta-analysis. METHODS: We performed a comprehensive literature search on January 14, 2016, using MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and Scopus. In addition, the references of all articles obtained were searched manually. The qualities of each study were assessed using the Newcastle-Ottawa quality assessment scale. The main outcomes were recurrence, disease-free survival (DFS), and overall survival (OS). We calculated the risk ratio (RR) and hazard ratio (HR) for the recurrence and survival rates, respectively. RESULTS: The RR of patients whose initial recurrences was local recurrence (LR), distant metastasis (DM), LR + DM, or overall recurrences were 0.18, 1.00, 0.61, and 0.49, respectively. There was no heterogeneity in the results. The HR of DFS was 0.59 and indicated that DFS in the TME group was superior compared with that in the W&S group. The OS has no significant difference between the studies. CONCLUSIONS: Although the W&S approach seemed feasible for rectal cancer patients with a cCR after neoadjuvant CCRT, concrete evidence obtained in well-controlled randomized trials with a long-term follow-up is required to validate potential treatment options.

Stereotactic Body Radiation Therapy for Low- to Intermediate-risk Prostate Adenocarcinoma.

The aim of the present study was to evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) for low- to intermediate-risk prostate adenocarcinoma. Thirty-nine patients were retrospectively reviewed. The SBRT was delivered using the CyberKnife with the fiducial tracking method combined with In-tempo imaging. The gross target volume, which included the prostate only, was delineated on the fused CT/MRI scans. The prescription dose was delivered every other day as 5 fractions of 7.5 Gy. Venous blood was obtained before and after SBRT to assess the prostate-specific antigen (PSA) level. Toxicity was evaluated using the CTCAE, v4.03. The median follow-up time was 30.0 months. The median initial PSA level was 7.7 ng/mL. PSA levels decreased in all patients treated with SBRT, and after 5 months, the median PSA was less than 2 ng/mL. The rate of overall 3-yr actuarial biochemical failure free survival was 93.9%. Acute side effects were generally comparable with those of previous studies. The PSA change and toxicity after SBRT for low- to intermediate-risk prostate adenocarcinoma indicates favorable biochemical responses and tolerable levels of toxicity. Additionally short course treatment may produce cost benefit and convenience to patients.

Combination effects of tissue heterogeneity and geometric targeting error in stereotactic body radiotherapy for lung cancer using CyberKnife.

We have investigated the combined effect of tissue heterogeneity and its variation associated with geometric error in stereotactic body radiotherapy (SBRT) for lung cancer. The treatment plans for eight lung cancer patients were calculated using effective path length (EPL) correction and Monte Carlo (MC) algorithms, with both having the same beam configuration for each patient. These two kinds of plans for individual patients were then subsequently recalculated with adding systematic and random geometric errors. In the ordinary treatment plans calculated with no geometric offset, the EPL calculations, compared with the MC calculations, largely overestimated the doses to PTV by ~ 21%, whereas the overestimation were markedly lower in GTV by ~ 12% due to relatively higher density of GTV than of PTV. When recalculating the plans for individual patients with assigning the systematic and random geometric errors, no significant changes in the relative dose distribution, except for overall shift, were observed in the EPL calculations, whereas largely altered in the MC calculations with a consistent increase in dose to GTV. Considering the better accuracy of MC than EPL algorithms, the present results demonstrated the strong coupling of tissue heterogeneity and geometric error, thereby emphasizing the essential need for simultaneous correction for tissue heterogeneity and geometric targeting error in SBRT of lung cancer.

Prostate-Specific Antigen (PSA) Bounces Following Stereotactic Body Radiotherapy for Prostate Cancer: Importance of PSA Test Frequency.

PURPOSE: Prostate-specific antigen (PSA) bounce is a common phenomenon that can be observed in patients of prostate cancer treated by radiotherapy. However, the clinical, pathological, or dosimetric predictors and clinical significance of PSA bounce in stereotactic body radiotherapy (SBRT) patients is still unknown. METHODS: Between August 2006 to December 2015, 74 prostate cancer patients were treated by SBRT with Cyberknife at two medical centers. The prescription dose was 35-37.5 Gy in 5 fractions. Follow-up PSA tests were more frequently performed in one hospital than the other (median 4 vs. 10 times for initial one year). PSA bounce was defined as a rise of 0.2 ng/mL followed by a decline to or below previous nadir. RESULTS: A total of 74 patients, PSA bounce was observed in 41 patients (55.4%). On univariate analysis, the treated medical center (p = 0.02), PSA follow-up frequency (p = 0.01), patient age (p < 0.01), and total prescription dose (p = 0.03) were significant clinical factors to predict the incidence of PSA bounce, while in multivariable analysis only the PSA follow-up frequency, and patient age remains significant. CONCLUSION: PSA bounce was seen in a significant proportion of patients after Cyberknife SBRT. The PSA follow-up test frequency, and patient age were significant factors that were correlated with the incidence of PSA bounces in this study.

Assessment of deep learning-based auto-contouring on interobserver consistency in target volume and organs-at-risk delineation for breast cancer: Implications for RTQA program in a multi-institutional study.

PURPOSE: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV. METHODS AND MATERIALS: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification. RESULTS: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5-19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs. CONCLUSION: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation.

Compensation method for respiratory motion in proton treatment planning for mobile liver cancer.

We evaluated the dosimetric effect of a respiration motion, and sought an effective planning strategy to compensate the motion using four-dimensional computed tomography (4D CT) dataset of seven selected liver patients. For each patient, we constructed four different proton plans based on: (1) average (AVG) CT, (2) maximum-intensity projection (MIP) CT, (3) AVG CT with density override of tumor volume (OVR), and (4) AVG CT with field-specific proton margin which was determined by the range difference between AVG and MIP plans (mAVG). The overall effectiveness of each planning strategy was evaluated by calculating the cumulative dose distribution over an entire breathing cycle. We observed clear differences between AVG and MIP CT-based plans, with significant underdosages at expiratory and inspiratory phases, respectively. Only the mAVG planning strategy was fully successful as the field-specific proton margin applied in the planning strategy complemented both the limitations of AVG and MIP CT-based strategies. These results demonstrated that respiration motion induced significant changes in dose distribution of 3D proton plans for mobile liver cancer and the changes can be effectively compensated by applying field-specific proton margin to each proton field.

Target movement according to cervical lymph node level in head and neck cancer and its clinical significance.

PURPOSE: To evaluate set-up error for head and neck cancer (HNC) patients according to each neck lymph node (LN) level. And clinical factors affecting set-up error were analyzed. MATERIALS AND METHODS: Reference points (RP1, RP2, RP3, and RP4) representing neck LN levels I to IV were designated. These RP were contoured on simulation computed tomography (CT) and cone-beam CT of 89 HNC patients with the same standard. After image registration was performed, movement of each RP was measured. Univariable logistic regression analyses were performed to analyze clinical factors related to measured movements. RESULTS: The mean value of deviation of all axes was 1.6 mm, 1.3 mm, 1.8 mm, and 1.5 mm for RP1, RP2, RP3, and RP4, respectively. Deviation was over 3 mm in 24 patients. Movement of more than 3 mm was observed only in RP1 and RP3. In RP1, it was related to bite block use. Movement exceeding 3 mm was most frequently observed in RP3. Primary tumor and metastatic LN volume change were clinical factors related to the RP3 movement. CONCLUSION: Planning target volume margin of 4 mm for neck LN level I, 3 mm for neck LN level II, 5 mm for neck LN level III, and 3 mm for neck LN level IV was required to include all movements of each LN level. In patients using bite block, changes in primary tumor volume, and metastatic LN volume were related to significant movement.

Treatment outcomes between concurrent chemoradiotherapy and combination of surgery, radiotherapy, and/or chemotherapy in stage III and IV maxillary sinus cancer: multi-institutional retrospective analysis.

PURPOSE: The incidence of maxillary sinus cancer (MSC) is extremely rare, representing less than 1% of all cancers. Because of its rarity, the management of locally advanced MSC is a challenging issue. The objective of the present study was to retrospectively compare the efficacy of 2 traditional treatment strategies, concurrent chemoradiotherapy (CCRT) versus combination of surgery and radiotherapy and/or chemotherapy (SRCT) in MSC. PATIENTS AND METHODS: From 1989 to 2010, 65 patients with histologically confirmed stage III or IVA/IVB were retrospectively analyzed. RESULTS: The median age of our subjects was 60 years (range 36 to 81). The present study involved 18 women (27.7%) and 47 men (72.3%). Of the 65 patients, 52 (80.0%) had squamous cell carcinoma. The TNM stage was stage III, as determined by the American Joint Committee on Cancer, 6th edition, in 27 patients (41.5%). Stage IVA or IVB was observed in 38 patients (58.5%). Of the 65 patients, 41 underwent treatment. Of these 41 patients, 26 and 15 patients underwent SRCT and CCRT, respectively. During the 75.6 months (range 6.4 to 249.4) of median follow-up, the median progression-free survival duration was 45.1 months (95% confidence interval 0.0 to 142.7). The 5-year overall survival rate was 64.8%. However, the patients who had undergone surgery had better progression-free survival (hazard ratio 2.363, 95% confidence interval 1.098 to 5.085, P = .028) and overall survival (hazard ratio 4.989, 95% confidence interval 1.646 to 15.118, P = .004). The SRCT group had a better progression-free survival (P = .043) and overall survival (P = .029) duration than did the CCRT group. CONCLUSION: SRCT might be superior to CCRT for locally advanced MSC. Additional studies comparing the treatment outcomes of CCRT with SRCT are warranted.

Comprehensive Analysis of Set-Up Gain of 6-Dimensional Cone-Beam CT Correction Method in Radiotherapy for Head and Neck and Brain Tumors.

This study quantitatively analyzed the gain of the six-dimensional (6D) cone-beam CT (CBCT) correction method compared with the conventional set-up method in 60 patients who underwent radiation treatment of head and neck and brain tumors. The correction gain of CBCT was calculated for the translational and rotational motion components separately and in combination to evaluate the individual and overall effects of these motion components. Using a statistical simulation mimicking the actual set-up correction process, the effective gain of periodic CBCT correction during the entire treatment fraction was analyzed by target size and CBCT correction period under two different correction scenarios: translation alone and full 6D corrections. From the analyses performed in this study, the gain of CBCT correction was quantitatively determined for each situation, and the appropriate CBCT correction strategy was suggested based on treatment purpose and target size.