Clinical evaluation of deep learning and atlas-based auto-segmentation for organs at risk delineation.

Manual delineation of organs at risk and clinical target volumes is essential in radiotherapy planning. Atlas-based auto-segmentation (ABAS) algorithms have become available and been shown to provide accurate contouring for various anatomical sites. Recently, deep learning auto-segmentation (DL-AS) algorithms have emerged as the state-of-the-art in medical image segmentation. This study aimed to evaluate the effect of auto-segmentation on the clinical workflow for contouring different anatomical sites of cancer, such as head and neck (H&N), breast, abdominal region, and prostate. Patients with H&N, breast, abdominal, and prostate cancer (n = 30 each) were enrolled in the study. Twenty-seven different organs at four sites were evaluated. RayStation was used to apply the ABAS. Siemens AI-Rad Companion Organs RT was used to apply the DL-AS. Evaluations were performed with similarity indices using geometric methods, time-evaluation, and qualitative scoring visual evaluations by radiation oncologists. The DL-AS algorithm was more accurate than ABAS algorithm on geometric indices for half of the structures. The qualitative scoring results of the two algorithms were significantly different, and DL-AS was more accurate on many contours. DL-AS had 41%, 29%, 86%, and 15% shorter edit times in the HnN, breast, abdomen, and prostate groups, respectively, than ABAS. There were no correlations between the geometric indices and visual assessments. The time required to edit the contours was considerably shorter for DL-AS than for ABAS. Auto-segmentation with deep learning could be the first step for clinical workflow optimization in radiotherapy.

Analysis of the relationship between prescribed dose and dosimetric advantage of real-time intraoperatively built custom-linked seeds in iodine-125 prostate brachytherapy.

BACKGROUND: The purpose of this study was to investigate the differences in the dosimetric advantage of using intraoperatively built custom-linked (IBCL) seeds between permanent iodine-125 (I-125) seed implantation (PI) alone and PI followed by external-beam radiation therapy (EBRT) for prostate cancer. METHODS: We reviewed the records of 62 patients with localized prostate cancer who received transperineal interstitial brachytherapy with I-125 using free seeds or IBCL seeds. Twenty-four low- and intermediate-risk patients underwent PI alone with the prescribed dose of 160 Gy, and 39 high-risk patients underwent PI with 110 Gy, followed by EBRT with 45 Gy (PI + EBRT). Intraoperative and post-implant dosimetric parameters 1 month after implantation were collected and analyzed. RESULTS: The numbers of patients implanted with free seeds and IBCL seeds were 14 (58.3%) and 10 (41.7%), respectively, in the PI group and 25 (65.8%) and 13 (34.2%), respectively, in the PI + EBRT group. In the PI group, although there were significant differences in prostate V100 (p = 0.003) and D90 (p = 0.009) and rectum V100 (p = 0.026) on intraoperative dosimetry, these differences were not found on post-implant dosimetry. In the PI + EBRT group, the dosimetric parameters of IBCL seeds, such as prostate V200 (p = 0.013) and V250 (p = 0.010) and urethra D30 (p = 0.038), were better than those of free seeds on intraoperative dosimetry. Furthermore, even on post-implant dosimetry, prostate D90 (p = 0.004), V150 (p = 0.001), and homogeneity index (HI, p = 0.001), as well as V200 (p = 0.001) and V250 (p = 0.020), and urethra D5 (p = 0.008) as well as D30 (p = 0.003) had a better dosimetric quality in IBCL seeds than in free seeds. There was no significant difference in the operation time between free seeds and IBCL seeds in each PI and PI + EBRT group. CONCLUSIONS: Our results reveal that greater dosimetric benefits could be obtained using IBCL seeds in the case of permanent implantation with a lower prescribed dose, such as PI + EBRT, rather than PI alone.

Safe and successful birth following pelvic radiotherapy for rectal mucosa-associated lymphoid tissue lymphoma: a case report.

BACKGROUND: Mucosa-associated lymphoid tissue lymphomas can occur in various parts of the body, and half of mucosa-associated lymphoid tissue lymphomas occur in the gastrointestinal tract. Gastric mucosa-associated lymphoid tissue lymphoma is the most common lymphoma of the gastrointestinal tract and primary rectal mucosa-associated lymphoid tissue lymphoma is very rare. Because of the high radiosensitivity of mucosa-associated lymphoid tissue lymphomas, this condition can be controlled with radiotherapy of approximately 30 Gy alone. However, ovarian dysfunction as an adverse event of radiotherapy for pelvic lesions can become a problem in girls and women. We report a case of a 28-year-old woman with rectal mucosa-associated lymphoid tissue lymphoma who safely gave birth to a baby following 30.6 Gy radiotherapy to her whole rectum. CASE PRESENTATION: A 28-year-old Japanese woman became aware of bloody stools and was diagnosed as having Lugano I rectal mucosa-associated lymphoid tissue lymphoma. She was referred to our institute and initiated on radiotherapy. However, she expressed a desire to bear children. We used horizontally opposed pair fields for radiotherapy to minimize the irradiation to her endometrium and ovary. A total dose of 30.6 Gy was given in 17 fractions of 1.8 Gy by 10-Megavolt X-ray linear accelerator. As a result, one-third of her uterus and half of her ovary were outside the irradiation field. After approximately 1 year of treatment, positive pregnancy was confirmed and finally she safely gave birth to a baby girl without congenital abnormalities. CONCLUSIONS: This report provides hope for girls and women who have undergone irradiation for pelvic mucosa-associated lymphoid tissue lymphomas and who desire to bear children.

The retrospective analysis of the relationship between prescribed dose and risk factor for seed migration in iodine-125 prostate brachytherapy.

PURPOSE: The aim was to determine the dose-specific incidence and predictors of seed loss/migration after permanent seed implantation (PI) for localized prostate cancer. MATERIALS AND METHODS: The records of 79 patients with T1c-T3a prostate cancer who underwent prostate brachytherapy with loose iodine-125 seeds were retrospectively reviewed. Of these patients, 33 with low or intermediate risk underwent PI with the prescribed dose of 160 Gy for the clinical target volume (CTV), and 46 with high risk underwent PI with 110 Gy for the CTV followed by external beam radiotherapy (EBRT) with 45 Gy. Each CTV was defined as a contoured prostate. After PI, the incidence of seed loss/migration was assessed by a series of radiographs. RESULTS: Seed migration occurred in 22 (0.479 %) of 4589 implanted seeds 1 month after implantation. In PI alone, the number of needles (P = 0.081) and the number of seeds (P = 0.071) showed a trend for a difference between those with and without seed loss. In PI + EBRT, there was a significant difference in the discrepancy between the seed numbers calculated by the nomogram and actually implanted (P = 0.032). CONCLUSIONS: It is suggested that the discrepancy in seed numbers might be the predictor for seed migration in PI with 110 Gy.

Impact of pretreatment whole-tumor perfusion computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography measurements on local control of non-small cell lung cancer treated with stereotactic body radiotherapy.

This study aimed to investigate the correlation between the average iodine density (AID) detected by dual-energy computed tomography (DE-CT) and the maximum standardized uptake value (SUVmax) yielded by [18F] fluorodeoxyglucose positron emission tomography (18F-FDG PET) for non-small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Seventy-four patients with medically inoperable NSCLC who underwent both DE-CT and 18F-FDG PET/CT before SBRT (50‒60 Gy in 5‒6 fractions) were followed up after a median interval of 24.5 months. Kaplan-Meier analysis was used to determine associations between local control (LC) and variables, including AID, SUVmax, tumor size, histology, and prescribed dose. The median AID and SUVmax were 18.64 (range, 1.18-45.31) (100 µg/cm3) and 3.2 (range, 0.7-17.6), respectively. No correlation was observed between AID and SUVmax Two-year LC rates were 96.2% vs 75.0% (P = 0.039) and 72.0% vs 96.2% (P = 0.002) for patients classified according to high vs low AID or SUVmax, respectively. Two-year LC rates for patients with adenocarcinoma vs squamous cell carcinoma vs unknown cancer were 96.4% vs 67.1% vs 92.9% (P = 0.008), respectively. Multivariate analysis identified SUVmax as a significant predictor of LC. The 2-year LC rate was only 48.5% in the subgroup of lower AID and higher SUVmax vs >90% (range, 94.4-100%) in other subgroups (P = 0.000). Despite the short follow-up period, a reduction in AID and subsequent increase in SUVmax correlated significantly with local failure in SBRT-treated NSCLC patients. Further studies involving larger populations and longer follow-up periods are needed to confirm these results.

Prognostic impact of average iodine density assessed by dual-energy spectral imaging for predicting lung tumor recurrence after stereotactic body radiotherapy.

The purpose of this study was to investigate the prognostic significance of average iodine density as assessed by dual-energy computed tomography (DE-CT) for lung tumors treated with stereotactic body radiotherapy (SBRT). From March 2011 to August 2014, 93 medically inoperable patients with 74 primary lung cancers and 19 lung metastases underwent DE-CT prior to SBRT of a total dose of 45-60 Gy in 5-10 fractions. Of these 93 patients, nine patients had two lung tumors. Thus, 102 lung tumors were included in this study. DE-CT was performed for pretreatment evaluation. Regions of interest were set for the entire tumor, and average iodine density was obtained using a dedicated imaging software and evaluated with regard to local control. The median follow-up period was 23.4 months (range, 1.5-54.5 months). The median value of the average iodine density was 1.86 mg/cm(3) (range, 0.40-9.27 mg/cm(3)). Two-year local control rates for the high and low average iodine density groups divided by the median value of the average iodine density were 96.9% and 75.7% (P = 0.006), respectively. Tumors with lower average iodine density showed a worse prognosis, possibly reflecting a hypoxic cell population in the tumor. The average iodine density exhibited a significant impact on local control. Our preliminary results indicate that iodine density evaluated using dual-energy spectral CT may be a useful, noninvasive and quantitative assessment of radio-resistance caused by presumably hypoxic cell populations in tumors.

Clinical outcome of stereotactic body radiotherapy for primary and oligometastatic lung tumors: a single institutional study with almost uniform dose with different five treatment schedules.

BACKGROUND: To evaluate clinical outcomes of stereotactic body radiotherapy (SBRT) for localized primary and oligometastatic lung tumors by assessing efficacy and safety of 5 regimens of varying fraction size and number. METHODS: One-hundred patients with primary lung cancer (n = 69) or oligometastatic lung tumors (n = 31), who underwent SBRT between May 2003 and August 2010, were included. The median age was 75 years (range, 45-88). Of them, 98 were judged to have medically inoperable disease, predominantly due to chronic illness or advanced age. SBRT was performed using 3 coplanar and 3 non-coplanar fixed beams with a standard linear accelerator. Fraction sizes were escalated by 1 Gy, and number of fractions given was decreased by 1 for every 20 included patients. Total target doses were between 50 and 56 Gy, administered as 5-9 fractions. The prescribed dose was defined at the isocenter, and median overall treatment duration was 10 days (range, 5-22). RESULTS: The median follow-up was 51.1 months for survivors. The 3-year local recurrence rates for primary lung cancer and oligometastasis was 6 % and 3 %, respectively. The 3-year local recurrence rates for tumor sizes ≤3 cm and >3 cm were 3 % and 14 %, respectively (p = 0.124). Additionally, other factors (fraction size, total target dose, and BED10) were not significant predictors of local control. Radiation pneumonia (≥ grade 2) was observed in 2 patients. Radiation-induced rib fractures were observed in 22 patients. Other late adverse events of greater than grade 2 were not observed. CONCLUSION: Within this dataset, we did not observe a dose response in BED10 values between 86.4 and 102.6 Gy. SBRT with doses between 50 and 56 Gy, administered over 5-9 fractions achieved acceptable tumor control without severe complications.

Stereotactic body radiotherapy for lung metastases as oligo-recurrence: a single institutional study.

The purpose of this study was to investigate clinical outcomes following stereotactic body radiotherapy (SBRT) for lung metastases as oligo-recurrence. From May 2003 to June 2014, records for 66 patients with 76 oligo-recurrences in the lungs treated with SBRT were retrospectively reviewed. Oligo-recurrence primary sites and patient numbers were as follows: lungs, 31; colorectal, 13; head and neck, 10; esophagus, 3; uterus, 3; and others, 6. The median SBRT dose was 50 Gy (range, 45-60 Gy) administered in a median of 5 (range, 5-9) fractions. All patients received SBRT, with no acute toxicity. Surviving patients had a median follow-up time of 36.5 months. The 3-year rates of local control, overall survival and disease-free survival were 90.6%, 76.0% and 53.7%, respectively. Longer disease-free interval from initial treatment to SBRT, and non-colorectal cancer were both associated with favorable outcomes. Disease progression after SBRT occurred in 31 patients, most with distant metastases (n = 24) [among whom, 87.5% (n = 21) had new lung metastases]. Among these 21 patients, 12 were judged as having a second oligo-recurrence. Additional SBRT was performed for these 12 patients, and all 12 tumors were controlled without disease progression. Three patients (4.5%) developed Grade 2 radiation pneumonitis. No other late adverse events of Grade ≥2 were identified. Thus, SBRT for oligo-recurrence achieved acceptable tumor control, with additional SBRT also effective for selected patients with a second oligo-recurrence after primary SBRT.

LW6, a hypoxia-inducible factor 1 inhibitor, selectively induces apoptosis in hypoxic cells through depolarization of mitochondria in A549 human lung cancer cells.

Hypoxia­inducible factor 1 (HIF­1) activates the transcription of genes that act upon the adaptation of cancer cells to hypoxia. LW6, an HIF­1 inhibitor, was hypothesized to improve resistance to cancer therapy in hypoxic tumors by inhibiting the accumulation of HIF­1α. A clear anti­tumor effect under low oxygen conditions would indicate that LW6 may be an improved treatment strategy for cancer in hypoxia. In the present study, the HIF­1 inhibition potential of LW6 on the growth and apoptosis of A549 lung cancer cells in association with oxygen availability was evaluated. LW6 was observed to inhibit the expression of HIF­1α induced by hypoxia in A549 cells at 20 mM, independently of the von Hippel­Lindau protein. In addition, at this concentration, LW6 induced hypoxia­selective apoptosis together with a reduction in the mitochondrial membrane potential. The intracellular reactive oxygen species levels increased in LW6­treated hypoxic A549 cells and LW6 induced a hypoxia­selective increase of mitochondrial O2•­. In conclusion, LW6 inhibited the growth of hypoxic A549 cells by affecting the mitochondria. The inhibition of the mitochondrial respiratory chain is suggested as a potentially effective strategy to target apoptosis in cancer cells.

Radiation-induced rib fracture after stereotactic body radiotherapy with a total dose of 54-56 Gy given in 9-7 fractions for patients with peripheral lung tumor: impact of maximum dose and fraction size.

BACKGROUND: Radiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor. METHODS: During 2003-2008, 41 patients with 42 lung tumors were treated with SBRT to 54-56 Gy in 9-7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study. RESULTS: Median follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16-48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10-55, age, sex, and planning target volume were not significantly different. CONCLUSIONS: The doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures.

Correlation between tumor size and blood volume in lung tumors: a prospective study on dual-energy gemstone spectral CT imaging.

The purpose of this study was to investigate the relationship between tumor size and blood volume for patients with lung tumors, using dual-energy computed tomography (DECT) and a gemstone spectral imaging (GSI) viewer. During the period from March 2011 to March 2013, 50 patients with 57 medically inoperable lung tumors underwent DECT before stereotactic body radiotherapy (SBRT) of 50-60 Gy in 5-6 fractions. DECT was taken for pretreatment evaluation. The region-of-interest for a given spatial placement of the tumors was set, and averages for CT value, water density and iodine density were compared with tumor size. The average values for iodine density in tumors of ≤ 2 cm, 2-3 cm, and >3 cm maximum diameter were 24.7, 19.6 and 16.0 (100 µg/cm(3)), respectively. The average value of the iodine density was significantly lower in larger tumors. No significant correlation was detected between tumor size and average CT value or between tumor size and average water density. Both the average water density and the average CT value were affected by the amount of air in the tumor, but the average iodine density was not affected by air in the tumor. The average water density and the average CT value were significantly correlated, but the average iodine density and the average CT value showed no significant correlation. The blood volume of tumors can be indicated by the average iodine density more accurately than it can by the average CT value. The average iodine density as assessed by DECT might be a non-invasive and quantitative assessment of the radio-resistance ascribable to the hypoxic cell population in a tumor.