A Recurrent Solitary Fibrous Tumor With an Exceptional Response to Low-Dose Radiotherapy: A Case Report and Literature Review.

Solitary fibrous tumor (SFT) is a soft tissue tumor derived from mesenchymal cells. We report a case of a giant SFT with insulin-like growth factor 2 (IGF-2) production in the pelvis of an 85-year-old male. SFT was diagnosed in surgery for a complaint of left lower abdominal distension. Subsequent tumor recurrence and progression caused rectal passage obstruction and hypoglycemia. Low-dose radiotherapy of 15 Gy in five fractions was started five years and four months after surgery, initially for a huge tumor around the rectum to improve rectal passage obstruction. The tumor volume shrank from 1054 cc before irradiation to 449 cc at one month and 396 cc at 10 months after irradiation. He had reached 90 years old at that time. Two months after the initial irradiation, similar radiotherapy of 15 Gy in five fractions was performed for a huge tumor in the right abdominal cavity. This tumor decreased from 1874 cc before irradiation to 615 cc at two months and 556 cc at seven months after irradiation. Dexamethasone (2.5 mg) was used for paraneoplastic syndrome at the time of initial radiation but was then reduced and became unnecessary two months after the second irradiation. Acute and late adverse events were mild. The patient is alive 60 months after the first irradiation. This case suggests that low-dose radiotherapy is beneficial as palliative therapy for symptom relief in patients with SFT.

Proton beam therapy combined with concurrent chemotherapy for esophageal cancer.

BACKGROUND/AIM: The aim of the present study was to evaluate the outcomes of proton beam therapy (PBT) concurrently combined with chemotherapy consisting of cisplatin and 5-fluorouracil for esophageal cancer. PATIENTS AND METHODS: Forty consecutive patients (stage I in 16 patients, II in 9 and III in 15) treated between 2008 and 2012 were evaluated. A total dose of 60 Gray equivalents (GyE) in 30 fractions was delivered, and an additional boost of 4-10 GyE was given when residual tumors were suspected. The median follow-up time was 24 months (range=7-66 months). RESULTS: No cardio-pulmonary toxicities of grade 3 or higher were observed. Recurrences were observed in 16 patients, and the 2-year rates of disease-specific survival and locoregional control were 77% and 66%, respectively. CONCLUSION: Irrespective of the small sample size and short follow-up time of the study, proton beam therapy combined with chemo therapy seems to be feasible for esophageal cancer.

Comparison of dose-volume histograms between proton beam and X-ray conformal radiotherapy for locally advanced non-small-cell lung cancer.

The purpose of this study was to compare the parameters of the dose-volume histogram (DVH) between proton beam therapy (PBT) and X-ray conformal radiotherapy (XCRT) for locally advanced non-small-cell lung cancer (NSCLC), according to the tumor conditions. A total of 35 patients having NSCLC treated with PBT were enrolled in this analysis. The numbers of TNM stage and lymph node status were IIB (n = 3), IIIA (n = 15) and IIIB (n = 17), and N0 (n = 2), N1 (n = 4), N2 (n = 17) and N3 (n = 12), respectively. Plans for XCRT were simulated based on the same CT, and the same clinical target volume (CTV) was used based on the actual PBT plan. The treatment dose was 74 Gy-equivalent dose (GyE) for the primary site and 66 GyE for positive lymph nodes. The parameters were then calculated according to the normal lung dose, and the irradiation volumes of the doses (Vx) were compared. We also evaluated the feasibility of both plans according to criteria: V5 ≥ 42%, V20 ≥ 25%, mean lung dose ≥ 20 Gy. The mean normal lung dose and V5 to V50 were significantly lower in PBT than in XCRT. The differences were greater with the more advanced nodal status and with the larger CTV. Furthermore, 45.7% of the X-ray plans were classified as inadequate according to the criteria, whereas 17.1% of the proton plans were considered unsuitable. The number of inadequate X-ray plans increased in cases with advanced nodal stage. This study indicated that some patients who cannot receive photon radiotherapy may be able to be treated using PBT.

Proton beam therapy for a patient with a giant thymic carcinoid tumor and severe superior vena cava syndrome.

Surgical resection is the first choice for treatment of a thymic carcinoid tumor and radiotherapy is often performed as adjuvant therapy. Here, we report a case of an unresectable and chemoresistant thymic carcinoid tumor that was treated successfully using standalone proton beam therapy (PBT). The patient was a 66-year-old woman in whom surgical resection of the tumor was impossible because of cardiac invasion. Therefore, chemotherapy was administered. However, the tumor grew to 15 cm in diameter and she developed severe superior vena cava (SVC) syndrome. She was referred to our hospital and received PBT at a dose of 74 GyE in 37 fractions. PBT was conducted without severe early toxicities. After PBT, the tumor mildly shrunk to 13 cm in diameter and SVC syndrome almost disappeared. Subsequently, the tumor has continued to decrease in size slowly over the last 2 years and late toxicities have not been observed. Our experience with this case suggests that PBT may be effective for an unresectable thymic carcinoid tumor.

Outcomes and prognostic factors for recurrence after high-dose proton beam therapy for centrally and peripherally located stage I non--small-cell lung cancer.

INTRODUCTION: This study was conducted to determine disease control rates and prognostic factors associated with recurrence of centrally and peripherally located stage I NSCLC treated using high-dose PBT. PATIENTS AND METHODS: Seventy-four patients with 80 centrally or peripherally located stage I NSCLCs were treated with PBT. A protocol using 72.6 Gy (RBE) in 22 fractions was used for centrally located tumors, and 66 Gy (RBE) in 10 or 12 fractions was used for peripherally located tumors. Data were collected and control rates and prognostic factors for recurrence were evaluated retrospectively. RESULTS: The median follow-up period was 31.0 months. The overall survival, disease-specific survival, and progression-free survival rates were 76.7%, 83.0%, and 58.6% at 3 years, respectively. Disease recurrence was noted in 30 patients and local recurrence of 11 tumors occurred. The 3-year local control rate was 86.2% for stage IA tumors and 67.0% for stage IB tumors. Radiation dose was identified as a significant prognostic factor for disease recurrence and local recurrence. Tumor diameter and age were only significantly associated with disease recurrence. The 3-year local control rate was 63.9% for centrally located tumors irradiated with 72.6 Gy (RBE) and 88.4% for peripherally located tumors irradiated with 66 Gy (RBE). CONCLUSION: Radiation dose was shown to be the most significant prognostic factor for tumor control in stage I NSCLC treated using high-dose PBT. Tumor diameter was not significant for local control. Further evaluation of PBT for centrally located tumors is warranted.

Designed-seamless irradiation technique for extended whole mediastinal proton-beam irradiation for esophageal cancer.

BACKGROUND: Proton-beam therapy (PBT) provides therapeutic advantages over conformal x-ray therapy in sparing organs at risk when treating esophageal cancer because of the fundamental physical dose distribution of the proton-beam. However, cases with extended esophageal lesions are difficult to treat with conventional PBT with a single isocentric field, as the length of the planning target volume (PTV) is longer than the available PBT field size in many facilities. In this study, the feasibility of a practical technique to effectively match PBT fields for esophageal cancer with a larger regional field beyond the available PBT field size was investigated. METHODS: Twenty esophageal cancer patients with a larger regional field than the available PBT single-field size (15 cm in our facility) were analyzed. The PTV was divided into two sections to be covered by a single PBT field. Subsequently, each PTV isocenter was aligned in a cranial-caudal (CC) axis to rule out any influence by the movement of the treatment couch in anterior-posterior and left-right directions. To obtain the appropriate dose distributions, a designed-seamless irradiation technique (D-SLIT) was proposed. This technique requires the following two adjustments: (A) blocking a part of the PTV by multi-leaf collimator(s) (MLCs); and (B) fine-tuning the isocenter distance by the half-width of the MLC leaf (2.5 mm in our facility). After these steps, the inferior border of the cranial field was designed to match the superior border of the caudal field. Dose distributions along the CC axis around the field junction were evaluated by the treatment-planning system. Dose profiles were validated with imaging plates in all cases. RESULTS: The average and standard deviation of minimum dose, maximum dose, and dose range between maximum and minimum doses around the field junction by the treatment-planning system were 95.9 ± 3.2%, 105.3 ± 4.1%, and 9.4 ± 5.2%. The dose profile validated by the imaging plate correlated with the results of the treatment-planning system in each case, with an error range within 4.3%. CONCLUSIONS: Dose distributions around the field junction were applied using D-SLIT. D-SLIT can be a useful treatment strategy for PBT of extended esophageal cancer.

Results of proton beam therapy without concurrent chemotherapy for patients with unresectable stage III non-small cell lung cancer.

INTRODUCTION: This study was performed retrospectively to evaluate the outcome of patients with stage III non-small cell lung cancer (NSCLC) after proton beam therapy (PBT) alone. METHODS: The subjects were 57 patients with histologically confirmed NSCLC (stage IIIA/IIIB: 24/33) who received PBT without concurrent chemotherapy. The cohort included 32 cases of squamous cell carcinoma, 18 adenocarcinoma, and 7 non-small cell carcinoma. Lymph node metastases were N0 7, N1 5, N2 30, and N3 15. Planned total doses ranged from 50 to 84.5 GyE (median, 74 GyE). RESULTS: Planned treatment was completed in 51 patients (89%). At the time of analysis, 20 patients were alive, and the median follow-up periods were 16.2 months for all patients and 22.2 months for survivors. The median overall survival period was 21.3 months (95% confidence interval: 14.2-28.4 months), and the 1- and 2-year overall survival rates were 65.5% (52.9-78.0%) and 39.4% (25.3-53.5%), respectively. Disease progression occurred in 38 patients, and the 1- and 2-year progression-free survival rates were 36.2% (23.1-49.4%) and 24.9% (12.7-37.2%), respectively. Local recurrence was observed in 13 patients, and the 1- and 2-year local control rates were 79.1% (66.8-91.3%) and 64.1% (47.5-80.7%), respectively. Grade ≥ 3 lung toxicity was seen in six patients, esophageal toxicity occurred at grade ≤ 2, and there was no cardiac toxicity. CONCLUSION: The prognosis of patients with unresectable stage III NSCLC is poor without chemotherapy. Our data suggest that high-dose PBT is beneficial and tolerable for these patients.

Novel chemoembolization using calcium-phosphate ceramic microsphere incorporating TNP-470, an anti-angiogenic agent.

The purpose of the present study was to develop a new method of chemoembolization to improve the therapeutic effectiveness and safety profile of cancer treatment. A chemoembolization approach was designed for human solid tumors using resorbable calcium-phosphate ceramic microspheres loaded with an agent anti-angiogenic to tumor vasculature in vivo. The human uterine sarcoma cell line FU-MMT-3 was used in this study because this tumor is aggressive and also exhibits a poor response to radiotherapy or any chemotherapy currently used. The calcium-phosphate ceramic microspheres loaded with TNP-470, an anti-angiogenic agent, were injected into FU-MMT-3 xenografts in nude mice three times per week for 8 weeks. The treatment using TNP-470-loaded microspheres suppressed tumor growth, compared to treatment with TNP-470 alone, microspheres alone, and the control. The mean tumor weight after treatment using TNP-470-loaded microspheres was significantly lower than that after treatment with microspheres alone. These ceramic microspheres were remarkably embolized in tumor microvessels as well as in the feeding arteries and a significant reduction of intratumoral vascularity was also demonstrated following treatment with TNP-470-loaded microspheres. Severe loss of body weight was not observed in any mice treated with the TNP-470-loaded microspheres, compared to treatment with TNP-470 alone. These results suggest that targeting tumor vasculature in human uterine sarcoma using calcium-phosphate microspheres might be more effective and safer than the treatment that employs anti-angiogenic agent alone. This new chemoembolization method incorporating an anti-angiogenic agent may contribute to the effective treatment of locally advanced or recurrent solid tumors.