Combination of Clinical Factors and Radiomics Can Predict Local Recurrence and Metastasis After Stereotactic Body Radiotherapy for Non-small Cell Lung Cancer.

BACKGROUND/AIM: Radiomics, which links radiological image features with patient prognoses, is expected to be applied for the prediction of the clinical outcomes of radiotherapy. We investigated the clinical and radiomic factors associated with recurrence patterns after stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We retrospectively analyzed 125 patients with histologically confirmed NSCLC who underwent SBRT between April 2003 and June 2017 at our institution. A radiomic score was calculated from five radiomics features (histogram and texture features) selected using the LASSO Cox regression model. These features were extracted from the gross tumor volume (GTV) in three-dimensional wavelet decomposition CT images. We used univariate and multivariate analyses to determine the associations between local control (LC) time and metastasis-free survival (MFS), clinical factors (age, sex, performance status, operability, smoking, histology, and tumor diameter), and the radiomic score. RESULTS: With a median follow-up of 37 months, the following 3-year rates were observed: overall survival, 80.9%; progression-free survival, 61.7%; LC, 75.1%, and MFS; 74.5%. In multivariate analysis, histology (squamous cell carcinoma vs. non-squamous cell carcinoma, p=0.0045), tumor diameter (>3 cm vs. ≤3 cm, p=0.039); and radiomic score (>0.043 vs. ≤0.043, p=0.042) were significantly associated with LC, and the radiomic score (>0.304 vs. ≤0.304, p<0.001) was significantly associated with MFS. CONCLUSION: Histology, tumor diameter, and radiomic score could be significant factors for predicting NSCLC recurrence patterns after SBRT.

Survival outcomes including salvage therapy of adult head and neck para-meningeal rhabdomyosarcoma: a multicenter retrospective study from Japan.

BACKGROUND: Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy. METHODS: We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy. RESULTS: Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 - 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 - 25.8 months): 17.1 months (95%CI: 6.0 - not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 - 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months-NR): 40.8 months (95%CI: 12.1 - NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions. CONCLUSION: The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions.

Similar-cases-based planning approaches with beam angle optimizations using water equivalent path length for lung stereotactic body radiation therapy.

This study aimed to propose automated treatment planning approaches based on similar cases with beam angle optimizations using water equivalent path length (WEPL) to avoid lung and rib doses for lung stereotactic body radiation therapy (SBRT). Similar cases to an objective case were defined as cases, which were close to the objective case with respect to the Euclidean distances based on geometrical features. Initial similar-case-based (ISC) plans were generated by applying lung SBRT plans of similar cases to objective cases. Similar cases were selected using the Euclidean distances based on lung shape and geometrical features from a radiation treatment planning database with 174 cases. Beam angles of the ISC plans were optimized using a greedy algorithm based on a cost function to include absorbed doses in the lung and ribs in the WEPL. The 12 dose evaluation indices for the planning target volume, lung, spinal cord, and ribs were evaluated in the original plans, ISC plans, and optimized similar-case-based (OSC) plans with and without WEPL for 20 test cases to investigate its dosimetric impact. These findings revealed that V10 and the mean dose for the lung and V20, V30, and V40 for the ribs in the OSC plan with WEPL improved more significantly than those in the original and ISC plans. This study indicates a potential of similar cases, whose beam angle configurations were optimized with WEPL to avoid lung and rib doses in lung SBRT plans.

Adverse Events of Concurrent Radiotherapy and ALK Inhibitors for Brain Metastases of ALK-Rearranged Lung Adenocarcinoma.

BACKGROUND: We investigated acute adverse events in patients with brain metastases (BMs) of anaplastic lymphoma kinase-rearranged (ALKr) non-small cell lung cancer (NSCLC) treated with both cranial radiotherapy and tyrosine kinase inhibitors (TKIs) of ALK. PATIENTS AND METHODS: Acute AEs were retrospectively investigated in patients with BMs of ALKr-NSCLC who received both whole-brain radiotherapy (WBRT) and ALK-TKI. For comparison, they were also assessed in patients with epidermal growth factor receptor (EGFR)-mutated NSCLC and wild-type with neither ALK rearrangement nor EGFR mutation treated with WBRT. RESULTS: Two ALKr cases were consequently eligible. Grade 3 otitis media unexpectedly occurred in both cases, while there was one case out of 11 and one case out of 18 of grade 2 otitis media among the EGFR-mutated cases and wild-type cases (p=0.013), respectively. CONCLUSION: Concurrent treatment with WBRT and ALK-TKI may be associated with acute severe ear toxicity in patients with BMs of ALKr-NSCLC.

Single-cycle induction chemotherapy for resectable advanced hypopharyngeal cancer.

BACKGROUND: The role of induction chemotherapy (IC) in the treatment of resectable advanced head and neck squamous cell carcinoma has not been elucidated, and the most effective IC regimen for chemoselection is still unknown. At our institute we have not used the triple combination of docetaxel, cisplatin, fluorouracil (TPF) for chemoselection, but rather the double combination of docetaxel + cisplatin (TP). The aim of this study is to report the outcome of patients with advanced hypopharyngeal cancer treated by single cycle of IC with TP followed by chemoradiation (CRT) or surgery. METHODS: A total of 29 patients with resectable advanced hypopharyngeal cancer who were treated with a single cycle of IC were entered into the study. Responders were treated by CRT while nonresponders underwent surgery. Outcomes were analyzed using the Kaplan-Meier method. RESULTS: A single cycle of IC with TP achieved response in 21 of the 29 patients. The major side effect was neutropenia which could be managed without delaying the sequential treatment. The 2-year overall survival and disease-specific survival were both 74.0% (stage III 100%, stage IVA 69.1%). The cumulative 2-year laryngeal preservation rate was 100% for stage III and 53.6% for stage IVA. CONCLUSION: A single cycle of IC with the combination of docetaxel + cisplatin may be sufficient to select advanced hypopharyngeal cancer patients with radio-sensitivity. IC intended for organ preservation strategies should be low toxic. Our strategy may be a useful for providing the benefits of IC and the opportunity for curative surgery without delay.

Cardiac metastasis of squamous cell carcinoma of the thyroid gland with severe disseminated intravascular coagulation: A case report.

Distant metastasis of primary squamous cell carcinoma (SCC) of the thyroid gland is rare and, to the best of our knowledge, cardiac metastasis has not been reported to date. A 57-year-old man underwent surgery and adjuvant chemoradiotherapy for stage IVA SCC of the thyroid gland. After 3 months, the patient was admitted to the Kyushu University Hospital (Fukuoka, Japan) with subcutaneous hematomas of the left thigh and lower leg, and he was diagnosed with cardiac and mediastinal lymph node metastases of SCC of the thyroid gland with severe disseminated intravascular coagulation (DIC). Echocardiography revealed a mass, 52 mm in greatest diameter, protruding from the interventricular septum towards the right ventricle. Weekly administration of paclitaxel and concurrent irradiation of the cardiac and lymph node metastases were performed. Eighteen days after the initiation of chemoradiotherapy, the DIC and hematomas had significantly improved, and the cardiac metastasis was stable. However, 2 months after admission, the patient developed dyspnea and multiple nodular shadows appeared to be spreading in the subpleura of the lungs bilaterally, which were initially suspected to be pulmonary tumor embolisms. Prednisolone and subsequent administration of lenvatinib were not effective and the patient succumbed to respiratory failure. Severe DIC caused by extremely rare cardiac metastasis of SCC of the thyroid gland was effectively controlled by chemoradiotherapy. However, intensive local control appears to be required for this condition.

Cataracts after Low-Dose Radiotherapy for Lymphoproliferative Disease of the Ocular Adnexa.

PURPOSE: To investigate the interval between low-dose radiotherapy and radiation-induced cataracts, and the factors affecting this interval, in patients with lymphoproliferative disease of the ocular adnexa. METHODS: A retrospective case series of 73 eyes of 59 patients who underwent radiotherapy from 1996 to 2005 with total doses ranging from 24 to 30 Gy was conducted. We investigated the relationships between the radiation-associated cataract formation intervals and age, gender, diabetes, and the use of corticosteroids. RESULTS: The mean interval was 36 months. None of the patients with lens shield developed cataracts. Age was inversely and significantly and gender was not significantly associated with the interval from first radiotherapy to cataract occurrence. The intervals did not differ significantly according to the presence of diabetes and corticosteroid therapy. CONCLUSIONS: The mean interval from the start of radiation therapy to radiation-related cataract formation was 36 months and age was a significant factor affecting this interval.

Prognostic Significance of a Minute Amount of Ascites During Chemoradiotherapy for Locally Advanced Pancreatic Cancer.

AIM: The aim of this study was to investigate the clinical factors for predicting overall survival (OS) and the significance of a minute amount of ascites on computed tomography (CT) in patients with locally advanced pancreatic cancer (LAPC) treated with chemoradiotherapy (CRT). PATIENTS AND METHODS: Between 2003 and 2011, 48 consecutive patients with LAPC were treated with CRT. Various clinical factors, including ascites, were evaluated for correlation with OS. A subset analysis of 16 patients with a minute amount of ascites was also performed. RESULTS: The median survival duration and the 1-year OS rates were 11.5 months and 50%, respectively. A minute amount of ascites on CT and elevated carbohydrate antigen 19-9 (CA19-9) level were significantly associated with poorer OS. In 16 patients with ascites, the amount of ascites increased in the course of the disease, and these were considered to be cancerous clinically, regardless of the amount. CONCLUSION: A minute amount of ascites and CA19-9 were important prognostic factors in CRT. Any amount of ascites was considered an early indicator of peritoneal carcinomatosis in LAPC.

Impact of Interstitial Changes on Radiation Pneumonitis After Stereotactic Body Radiation Therapy for Lung Cancer.

AIM: The aim of the present study was to evaluate the impact of interstitial changes (IC) on radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for lung cancer. PATIENTS AND METHODS: We analyzed 260 consecutive patients with primary lung cancer treated with SBRT. According to the presence or absence of IC on the pre-treatment computed tomography, patients were divided into two groups: an IC group (n=18) and a non-IC group (n=242). RESULTS: RP of grade 2 or more was observed in 9 (50.0%) and 14 (6.7%) patients in the IC and non-IC group, respectively. All three patients with grade 5 RP were in the IC group. As indicated by multivariate analysis, the presence of IC was the only significant predictive factor of RP of grade 2 or more. CONCLUSION: The presence of IC was a significant indicator of grade 2 or more RP after SBRT for patients with lung cancer.

Treatment Planning Comparison for Carbon Ion Radiotherapy, Proton Therapy and Intensity-modulated Radiotherapy for Spinal Sarcoma.

BACKGROUND/AIM: Carbon ion radiotherapy (CIRT), proton therapy (PT) and intensity-modulated radiotherapy (IMRT) are new radiation modalities suitable for treatment of spinal sarcomas. The objective of the study was to compare the treatment planning of these modalities. PATIENTS AND METHODS: We conducted a treatment planning comparison of the three modalities using a phantom imitating a spinal sarcoma and then six actual cases with spinal tumors. A uniform biological effective dose (BED) of 90 Gy10 was prescribed in previously reported fractionation schedules for each modality. The surface/center spinal cord dose constraints were set to BED of 96/77 Gy(E)3, respectively. RESULTS: CIRT achieved better homogeneity of dose distribution and coverage of target than PT independently of tumor extent around the spinal cord. In IMRT plans, the spinal cord dose was higher than that under CIRT and PT and coverage of the target deteriorated depending on the tumor extension. CONCLUSION: CIRT was most appropriate for the treatment of advanced spinal sarcomas.

Retrospective Analysis of Concurrent Chemoradiation with Triweekly Cisplatin plus 5-Fluorouracil Versus Weekly Cisplatin in Cervical Cancer.

BACKGROUND/AIM: Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced cervical cancer. The purpose of the study was to compare the outcomes of triweekly cisplatin plus 5-fluorouracil and weekly cisplatin regimens. PATIENTS AND METHODS: We retrospectively reviewed data from 91 patients with stage IB1-IVA cervical cancer. RESULTS: Out of 91 patients, 48 received triweekly CCRT and 43 received weekly CCRT. For triweekly CCRT, patients received a median of two chemotherapy cycles and median total doses of cisplatin and 5-fluorouracil were 210 mg/body and 8,525 mg/body, respectively. For weekly CCRT, patients received a median of five chemotherapy cycles and the median total dose of cisplatin was 252 mg/body. No statistically significant differences in overall survival or progression-free survival were noted between the two groups. CONCLUSION: Both triweekly CCRT and weekly CCRT appear to have similar efficacy for cervical cancer patients, but the toxicities were better tolerable in weekly CCRT.

Treatment Outcome of Radiotherapy for Localized Primary Ocular Adnexal MALT Lymphoma--Prognostic Effect of the AJCC Tumor-Node-Metastasis Clinical Staging System.

AIM: To analyze the treatment outcome of radiotherapy for localized primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML) and evaluate the prognostic effect of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) clinical staging system for POAML. PATIENTS AND METHODS: Seventy-three patients with Ann Arbor stage IE POAML who were treated with radiotherapy alone were analyzed. T-Factor based on the AJCC staging system was T1 in 28, T2 in 33 and T3 in 12 patients. RESULTS: Out of nine patients with relapse, six had distant and three had contralateral ocular adnexal relapse. One patient died of lymphoma progression. The 5-year local control and progression-free survival (PFS) rates were 100% and 81.5%, respectively. T-Factor was not significantly associated with PFS. CONCLUSION: Radiotherapy achieved excellent local control and survival rates for stage IE POAML. The AJCC TNM clinical staging system was not significantly predictive for PFS of stage IE POAML.

Clinical characteristics and outcome of pneumothorax after stereotactic body radiotherapy for lung tumors.

BACKGOUND: We retrospectively investigated the clinical characteristics and outcome of pneumothorax after stereotactic body radiotherapy (SBRT) for lung tumors. METHODS: Between April 2003 and July 2012, 473 patients with lung tumors were treated with SBRT. We identified 12 patients (2.5 %) with pneumothorax caused by SBRT, and evaluated the clinical features of pneumothorax. RESULTS: All of the tumors were primary lung cancers. The severity of radiation pneumonitis was grade 1 in 10 patients and grade 2 in two patients. Nine patients had emphysema. The planning target volume and pleura overlapped in 11 patients, and the tumors were attached to the pleura in 7 patients. Rib fractures were observed in three patients before or at the same time as the diagnosis of pneumothorax. The median time to onset of pneumothorax after SBRT was 18.5 months (4-84 months). The severity of pneumothorax was grade 1 in 11 patients and grade 3 in one patient. CONCLUSION: Although pneumothorax was a relatively rare late adverse effect after SBRT, some patients demonstrated pneumothorax after SBRT for peripheral lung tumors. Although most pneumothorax was generally tolerable and self-limiting, careful follow-up is needed.

Stereotactic body radiation therapy for primary lung cancers clinically diagnosed without pathological confirmation: a single-institution experience.

BACKGROUND: Pathological diagnosis of small lung lesions is sometimes difficult in medically inoperable patients. The purpose of this study was to evaluate the adverse events and the outcomes of stereotactic body radiation therapy (SBRT) for lung lesions which were clinically diagnosed as primary lung cancer without pathological confirmation. METHODS: Between April 2003 and April 2011, 88 patients with small lung lesions which were clinically diagnosed as primary lung cancer were treated with SBRT. The median tumor size was 19 mm (range 8-40 mm). The radiation dose was 48 Gy in four fractions in all patients. The median follow-up was 23 months (range 6-91 months). RESULTS: Recurrence was observed in 13 patients. The local control rate, progression-free survival rate, and overall survival rate at 3 years were 90, 67, and 80 %, respectively. Two patients (2.3 %) had Grade 2 radiation pneumonitis, and six patients (6.8 %) had Grade 2 rib fractures. There were no adverse events of Grade 3 or greater. CONCLUSIONS: SBRT appears to be a safe and effective treatment option for small lung lesions that are clinically diagnosed as primary lung cancer without pathological confirmation.

Recent advances in radiation oncology: intensity-modulated radiotherapy, a clinical perspective.

Radiotherapy plays an important role in the treatment of various malignancies, and intensity-modulated radiotherapy (IMRT) is an attractive option because it can deliver precise conformal radiation doses to the target while minimizing the dose to adjacent normal tissues. IMRT provides a highly conformal dose distribution by modulating the intensity of the radiation beam. A number of malignancies have been targeted by IMRT; this work reviews published data on the major disease sites treated with IMRT. The dosimetric advantage of IMRT has resulted in the significant reduction of adverse effects in some tumors. However, there are few clinical trials comparing IMRT and three-dimensional conformal radiotherapy (3D-CRT), and no definite increase in survival or the loco-regional control rate by IMRT has been demonstrated in many malignancies. IMRT also requires greater time and resources to complete compared to 3D-CRT. In addition, the cost-effectiveness of IMRT versus 3D-CRT has not yet been established.

Acute urinary morbidity after a permanent 125I implantation for localized prostate cancer.

We evaluated the predictive factors of acute urinary morbidity (AUM) after prostate brachytherapy. From November 2005 to January 2007, 62 patients with localized prostate cancer were treated using brachytherapy. The (125)Iodine ((125)I) seed-delivering method was a modified peripheral pattern. The prescribed dose was 144 Gy. Urinary morbidity was scored at 3 months after implantation. The clinical and treatment parameters were analysed for correlation with AUM. In particular, in this study, Du90 (the minimal dose received by 90% of the urethra), Dup90 (the minimal dose received by 90% of the proximal half of the urethra on the bladder side) and Dud90 (the minimal dose received by 90% of the distal half of the urethra on the penile side) were analysed. We found that 43 patients (69.4%) experienced acute urinary symptoms at 3 months after implantation. Of them, 40 patients had Grade 1 AUM, one patient had Grade 2 pain, and two patients had Grade 2 urinary frequency. None of the patients had ≥Grade 3. Univariate and multivariate analysis revealed that Du90 and Dup90 were significantly correlated with AUM. In this study, Du90 and Dup90 were the most significant predictors of AUM after prostate brachytherapy.

Radiotherapy for early-stage primary ocular adnexal mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML) is a rare disease. The purpose of this study was to evaluate the treatment outcome and patterns of failure of patients with early-stage POAML treated with radiotherapy. PATIENTS AND METHODS: From 1995 to 2008, 53 patients with early-stage POAML were reviewed. Tumors were categorized as either superficial or mass-forming type. In principle, superficial lesions (n=11) were treated with 24 Gy, while the mass-forming lesions (n=42) were irradiated with 30 Gy. The median follow-up period was 3.9 years. RESULTS: All four cases of relapse had mass-forming lesions. The 5-year overall and progression-free survival rates were 100% and 91.5%, respectively. Although 30 patients experienced grade 2 or 3 late adverse events, no patients had radiation-related retinopathy. CONCLUSION: Early-stage POAML can be well-controlled with radiotherapy. However, the risk of distant relapse should be noted, in particular, for mass-forming tumors.

Definitive fractionated re-irradiation for local recurrence following stereotactic body radiotherapy for primary lung cancer.

AIM: To retrospectively evaluate the efficacy and safety of definitive fractionated re-irradiation for local recurrence following stereotactic body radiotherapy (SBRT) for primary lung cancer. PATIENTS AND METHODS: Between April 2003 and December 2011, 398 patients with primary lung tumor underwent SBRT at the Kyushu University Hospital, and 46 out of these developed local recurrence after SBRT. Definitive fractionated re-irradiation was performed for 17 out of the 46 patients. The median dose of re-irradiation was 60 Gy/ 30 fractions. Concurrent chemotherapy was given to four patients. RESULTS: The median follow-up duration was 12.6 months. At one year post-re-irradiation, local progression-free survival was 33.8%; progression-free survival, 30.9%; cause-specific survival, 79.3%; and overall survival, 74.7%. No severe adverse events were observed during the follow-up. CONCLUSION: Definitive fractionated re-irradiation is thought to be a safe alternative therapy for local recurrence following SBRT, although its efficacy may be not entirely satisfactory.