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Background: The applicability of ultra-hypofractionated (ultra-HF) whole-breast irradiation (WBI) remains unknown in Japanese women. This study aimed to evaluate the safety and efficacy of this approach among Japanese women and report the results of an interim analysis performed to assess acute adverse events (AEs) and determine whether it was safe to continue this study. Methods: We enrolled Japanese women with invasive breast cancer or ductal carcinoma in situ who had undergone breast-conserving surgery, were aged ≥ 40 years, had pathological stages of Tis–T3 N0–N1, and had negative surgical margins. Ultra-HF-WBI was delivered at 26 Gy in five fractions over one week. When the number of enrolled patients reached 28, patient registration was paused for three months. The endpoint of the interim analysis was the proportion of acute AEs of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) within three months. Results: Of the 28 patients enrolled from seven institutes, 26 received ultra-HF-WBI, and 2 were excluded due to postoperative infections. No AEs of grade ≥ 3 occurred. One patient (4%) experienced grade 2 radiation dermatitis, and 18 (69%) had grade 1 radiation dermatitis. The other acute grade 1 AEs experienced were skin hyperpigmentation (n = 10, 38%); breast pain (n = 4, 15%); superficial soft tissue fibrosis (n = 3, 12%); and fatigue (n = 1, 4%). No other acute AEs of grade ≥ 2 were detected. Conclusions: Acute AEs following ultra-HF-WBI were within acceptable limits among Japanese women, indicating that the continuation of the study was appropriate. [ABSTRACT FROM AUTHOR]

Summary: Introduction/Background Durvalumab demonstrated a good efficacy and safety in patients with unresectable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT) in the PACIFIC trial. Although a history of radiation pneumonitis (RP) has been reported to increase the risk of pneumonitis associated with programmed death-1 inhibitors, the safety and efficacy of durvalumab in patients with baseline Grade 1 RP have not been assessed. Therefore, we carried out a multicenter prospective cohort study to evaluate the efficacy and safety of durvalumab in these patients. Patients and Methods This was a multicenter prospective cohort study of 35 patients with Grade 1 RP after CCRT and before durvalumab initiation. This study was a first prespecified analysis for the first 20 patients with the primary objective of assessing the short-term safety; it was assessed 3 months after durvalumab initiation. Results Twenty patients were enrolled in this study between March 1, 2019, and September 3, 2019. Three patients (15%) experienced drug-related Grade ≥3 adverse events, while three patients (15%) had Grade ≥2 pneumonitis/RP within 3 months after durvalumab initiation. Three months after durvalumab initiation, all the patients were alive and four patients (20%) experienced disease progression. Conclusion Durvalumab can be a feasible treatment option for patients with stage III NSCLC with baseline Grade 1 RP following CCRT. (Trial registration number: UMIN000036061. The registration period was between March 2019 and December 2019.) [ABSTRACT FROM AUTHOR]

Purpose: Recently, based on results of the PACIFIC trial, durvalumab after chemoradiotherapy (CRT) became the standard therapy for unresectable stage III non-small cell lung cancer (NSCLC). However, in the PACIFIC trial, patients were recruited and randomized after CRT, and certain patients were considered ineligible after CRT in the real world. No study has been conducted on the patients who were ineligible for the PACIFIC trial, and hence, we conducted a retrospective study on them.Methods: We identified 82 patients with stage III NSCLC who received definitive platinum-based concurrent CRT and had World Health Organization performance status of 0-1. We investigated the proportion, clinical characteristics, and prognoses of patients who became ineligible for the PACIFIC trial after CRT.Results: After CRT, 19 of 82 patients (23%) became ineligible for the PACIFIC trial. Comparison between eligible and ineligible patients revealed that old age (p = 0.042), male gender (p = 0.031), and radiation therapy with V20 ≥ 35% (p = 0.032) were associated with ineligibility after CRT. Moreover, ineligible patients showed shorter PFS (6.6 vs. 15.7 months, hazard ratio [HR] 2.61, 95% confidence interval [CI] 1.16-5.89, p = 0.016) and shorter OS (18.6 vs. 44.3 months, HR 3.03, 95% CI 1.29-7.10, p = 0.007) than eligible patients.Conclusions: Our study revealed the clinical characteristics and prognoses of patients who became ineligible for the PACIFIC trial after CRT. Physicians should be careful while prescribing CRT for patients with characteristics such as old age, male gender, and radiation therapy with V20 ≥ 35%. [ABSTRACT FROM AUTHOR]

Background: To investigate the maximum tolerated dose (MTD) and recommended dose (RD) of stereotactic body radiation therapy (SBRT) for centrally located stage IA non-small cell lung cancer (NSCLC). Methods: Five dose levels, ranging from of 52 to 68 Gy in eight fractions, were determined; the treatment protocol began at 60 Gy (level 3). Each dose level included 10 patients. Levels 1-2 were indicated if more than four patients exhibited dose-limiting toxicity (DLT), which was defined as an occurrence of a grade 3 (or worse) adverse effect within 12 months after SBRT initiation. MTD was defined as the lowest dose level at which more than four patients exhibited DLT. Results: Ten patients were enrolled in the level 3 study. One patient was considered unsuitable because of severe emphysema. Therefore, nine patients were evaluated and no patient exhibited DLT. The level 3 results indicated that we should proceed to level 4 (64 Gy). However, due to the difficulty involved in meeting the dose constraints, further dose escalation was not feasible and the MTD was found to be 60 Gy. Conclusions: The RD of SBRT for centrally located stage IA NSCLC was 60 Gy in eight fractions. [ABSTRACT FROM AUTHOR]

Purpose: When treating large metastatic brain tumors with stereotactic radiotherapy (SRT), high dose conformity to target is difficult to achieve. Employing a modified planning target volume (mPTV) instead of the original PTV may be one way to improve the dose distribution in linear accelerator-based SRT using a dynamic conformal technique. In this study, we quantitatively analyzed the impact of a mPTV on dose distribution.Materials and Methods: Twenty-four tumors with a maximum diameter of >2 cm were collected. For each tumor, two plans were created: one used a mPTV and the other did not. The mPTV was produced by shrinking or enlarging the original PTV according to the dose distribution in the original plan. The dose conformity was evaluated and compared between the plans using a two-sided paired t test.Results: The conformity index defined by the Radiation Therapy Oncology Group was 1.34 ± 0.10 and 1.41 ± 0.13, and Paddick's conformity index was 0.75 ± 0.05 and 0.71 ± 0.06, for the plans with and without a mPTV, respectively. All of these improvements were statistically significant (P < 0.05).Conclusion: The use of a mPTV can improve target conformity when planning SRT for large metastatic brain tumors. [ABSTRACT FROM AUTHOR]

Although breast-conserving surgery followed by definitive irradiation is an established treatment for patients with early breast cancer, the role of breast-conserving therapy (BCT) for patients with bilateral breast cancer has not been well studied and the radiation therapy technique is still under investigation. We examined the feasibility of breast-conserving therapy for bilateral breast cancer and present here our radiation therapy technique with CT simulator. Between July 1990 and December 1998, we treated 17 patients with bilateral breast cancer who underwent bilateral breast-conserving surgery followed by definitive irradiation. Seven patients had synchronous bilateral breast cancer and ten had metachronous bilateral breast cancer. Radiation therapy consisted of 50 Gy to the bilateral whole breast in all patients but one. A CT simulator was used to plan a tangential radiation field to the breast in all patients. Boost irradiation of 10 Gy was administered to 8 tumors with close or positive margins. With a median follow-up periods of 95 months from each operation, no patients showed locoregional recurrence on either side, and none suffered distant metastasis. Furthermore no serious late adverse effects were observed. This study demonstrated that BCT is feasible for bilateral breast cancer and the CT simulator is useful for determining the radiation field, especialy when lesions are metachronous. [ABSTRACT FROM AUTHOR]

To evaluate the influence of boost irradiation for breast conserving therapy on skin and subcutaneous tissue. Between 1989 and 1995, 468 patients were treated with breast conserving surgery (quadrantectomy or wide excision with axillary dissection) followed by 50 Gy whole breast irradiation. Among them, fifty-eight patients with positive or close margins were treated with 10 Gy external beam boost irradiation. Skin and subcutaneous soft tissue changes during 5-years of follow-up were examined by inspection and palpation and evaluated using the BCT follow-up form based on EORTC late effect toxicity scoring. Four percent (20/468) of the patients showed grade 2 late changes in skin and soft tissue. Four of them had skin telangiectasis, which was limited to within the boost field. Boost irradiation had no definite influence on other late changes. Patients’ age, extent of surgery, and pT size had no significant relation to the late changes. The cosmetic score 5 years after BCT was not significantly different between the patients with and without boost irradiation. Although 10 Gy boost irradioation after 50 Gy whole breast irradiation increased skin telangiectasis, the late skin and soft tissue changes caused by the boost irradiation were generally mild and there was no substantial deterioration of cosmetic outcome. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine whether boost irradiation relying on radiopaque clips placed surgically around the resected margin of breast cancer contributes to increasing the local control rate in patients with close or positive margins in breast-conserving therapy (BCT). Among 837 patients with breast cancer who underwent BCT between November 1987 and December 1998, 181 patients with close or positive surgical margins received boost irradiation following conventional tangential whole breast irradiation. Since 1994, four radiopaque clips were surgically placed around the resected margin of the breast cancer in 155 patients treated with wide excision. The four clips were clearly and accurately identified with a CT-simulator (CT-S). The boost irradiation field was automatically determined with a safety margin of 3 cm according to one-to-one correspondence of radiopaque clips to pathologically close or positive surgical margins. In the remaining 26 patients treated before 1994, the boost irradiation field was determined according to the skin tattoo of the primary tumor. The median follow-up period of the 155 patients receiving the radiopaque clips was 42 months (range: 19 to 78), and that of the 26 patients without the clips was 87 months. Local recurrence was observed in two of the 155 patients who underwent boost irradiation using the radiopaque clips 39 and 54 months after the surgery, while 4 of the 26 patients developed local recurrence 14, 23, 51, and 76 months after BCT. In three of the four patients without the clips developing local recurrences, local recurrences were observed at the margin of the boost irradiation field. The 5-year local recurrence-free survival rate of patients who received boost irradiation with the radiopaque clips was 97%, and that of patients without the clips was 88%. The difference of local recurrence-free survival rates between the patients with and without the clips was significant (p<0.05). Surgically placed radiopaque clips appear to be useful for determining adequate boost field in the BCT using the CT-S and help increase the local control rate. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the results of breast-conserving therapy (BCT), defined as the combination of breast-conserving surgery with axillary dissection and definitive radiation therapy for ductal carcinoma in situ (DCIS). Between November 1987 and March 1998, 33 patients with DCIS undergoing BCT at our hospital were examined. The mean age was 48. All patients underwent quadrantectomy or wide excision as well as axillary dissection. Radiation therapy consisted of 50 Gy to the ipsilateral whole breast. Boost irradiation of 10 Gy was given to 15 patients with close or positive margins. Nearly all patients received adjuvant chemotherapy with 5-fluorouracil or its derivatives and adjuvant endocrine therapy with tamoxifen for 2 years. The minimum and median follow-up periods were 32 and 80 months, respectively. All patients but one were followed. Only one patient had a non-invasive local recurrence, 23 months after her operation. This patient was salvaged with simple mastectomy. Her prognostic index score was 8. The five-year local control rate was 97%. No serious acute or late complications were noted. The results of this retrospective study substantiate favorable data and appear to confirm the efficacy and reasonable local recurrence rate of BCT for the treatment of DCIS. [ABSTRACT FROM AUTHOR]

Meningeal carcinomatosis (MC) is an uncommon but aggressive complication of advanced breast cancer with a recently increasing incidence. Although the prognosis is extremely poor for MC patients, early diagnosis and appropriate treatment are important. Subjects and Methods: We reviewed 8 cases of MC from breast cancer at Kyoto University Hospital from 1990 to 1999. The median age was 51.5 years. All patients had widespread systemic metastases when diagnosed with MC. clinical symptoms were categorized into 3 groups: cranial nerve symptoms, spinal nerve symptoms, and other symptoms. Imaging studies were positive for MC in only 4 patients. Initial CSF cytology studies were positive in 4 patients, and repeated CSF cytology yielded positive results in the remaining 4 patients. Thus the median interval between the onset of any clinical symptom of MC and the initiation of treatment was 22.5 days (range 7 to 120 days ). All patients received whole brain radiotherapy (WBRT). Four patients were given intrathecal chemotherapy and/or intrathecal immunotherapy in addition to WBRT Improvement of cranial nerve symptoms, spinal nerve symptoms, and other symptoms were observed in 3/5, 1/3, and 5/7 patients, respectively. Patients with cranial nerve symptoms who started WBRT within 29 days of the onset of the symptoms showed at least partial recovery whereas patients who started WBRT later showed no recovery. The median survival was 123 days (53 to 310 days). MC was the direct cause of death in 1 of 8 patients When MC is clinically suspected, neither a negative imaging study nor a single negative CSF cytology can rule out MC. Prompt initiation of WBRT with or without intrathecal chemotherapy may be important for recovery from cranial nerve symptoms [ABSTRACT FROM AUTHOR]

The purpose of this study is to determine and recommend the optimal radiation source according to breast size for tangential irradiation in breast conserving therapy. Twenty-eight patients treated at our department from January 1994 to January 1996 were studied. The dose distribution within the irradiated breast was calculated using ap60Co-gamma ray and 6 MV-X ray. Then we compared 3-D dose distributions of thep60Co-gamma ray and 6 MV-X ray in differentsized breasts. Three parameters (breast volume, chest wall separation, and breast height) were adopted as representative of breast size. We also examined correlations among the three parameters. When the breast size was large (breast volume>400 cmp3, chest wall separation >19.5 cm, or breast height>6.5 cm), the average volume of normal tissue which received more than 110% of the isocenter dose (“hot spot”) was significantly greater with thep60Co-gamma ray than with the 6 MV-X ray (p<0.05). A similar result was obtained with regard to hot spots in the clinical target volume. The cold area that received less than 95% of the isocenter dose was greater using a 6 MV-X ray when the breast size was small (breast volume <200 cmp3, chest wall separation< 17.5 cm, or breast height <5.0 cm). However, the difference was not significant. There was a significant correlation between breast volume and chest wall separation (r=0.849, p< 0.001). Breast volume and breast height were also significantly correlated (r=0.813, p<0.001). Since breast volume and shape are different in each patient, the optimal energy should be selected for each case to obtain uniform dose distribution in breast-conserving therapy. Chest wall separation or breast height, which are measurable without a 3-D planning system, can substitute for breast volume as parameters for breast size. We recommend that thep60Co-gamma ray not be used for treating large breasts, those with chest wall separation>/= 19.5 cm or breast height>/=6.5 cm. [ABSTRACT FROM AUTHOR]

Results of radiation therapy for 20 patients with recurrent meningioma were analyzed. The patients included 8 men and 12 women, with a median age of 55 years. All of the patients had undergone at least one operation prior to the reoperation preceding radiotherapy. Ten patients had benign meningiomas, while 4 and 6 patients had atypical and malignant meningiomas, respectively, at the time of radiotherapy. The median radiation dose was 59.4 Gy (range: 50–61.2 Gy). The local control rate at 5 years was 36% for all 20 patients (41% for benign meningiomas and 30% for atypical or malignant meningiomas). The 5-year survival rate was 47%. Excluding 2 patients whose follow-up period was shorter than the preradiotherapy interval from the previous operation, the postradiation recurrence-free period was longer than the preradiotherapy interval in 50% (9/18) of the patients. No serious complications of radiotherapy were observed. Radiotherapy seemed to be effective in controlling the tumor or delaying recurrence in at least half of the patients. However, higher doses of radiation, using sophisticated radiation techniques, may be necessary to obtain higher control rates. [ABSTRACT FROM AUTHOR]

Purpose. Local control for pituitary adenomas treated with external beam radiation therapy was retrospectively analyzed to evaluate the efficacy of radiation. Materials and methods. Thirty-eight patients treated with radiation therapy between 1979 and 1994 were analyzed. The median age was 46. Nineteen newly diagnosed tumors were treated with surgery and radiation therapy, while the others were recurrent cases. Twenty-two tumors were non-functioning, while 10 produced growth hormone (GH) and three each were prolactin-, and adrenocorticotropic hormone (ACTH)-producing tumors. The median radiation dose was 50 Gy in 25 fractions. Results. Non-functioning adenomas and prolactin-producing adenomas were completely controlled, judging from the absence of tumor progression on neuroimaging studies and clinical symptoms, and normalization of the serum prolactin level ( <25 ng/ml). On the other hand, local control was obtained in only one of the 3 patients with ACTH-producing adenomas, and the control rate at 10 years was only 46% for GH-producing adenomas. Panhypopituitarism developed in 35% of the patients after radiation therapy. No other serious complications were noted. Conclusion. Non-functioning pituitary adenomas and prolactin-producing adenomas were well controlled with external radiation therapy combined with surgery. However, dose escalation might be necessary to control GH- or ACTH-producing tumors. It is important to replace corticosteroid hormone and thyroid hormone in many patients. [ABSTRACT FROM AUTHOR]

The cosmetic and functional results of breast conserving therapy for early breast cancer were evaluated. These are important endpoints in the assessment of breast conserving therapy in addition to tumor control and survival. The factors suspected to influence cosmesis were also analyzed. In 206 patients with stage I and II breast cancer treated by wide excision and axillary dissection followed by radiation therapy, the cosmetic results and complications were analyzed. The cosmetic outcome was assessed by a scoring method and breast retraction assessment (BRA). As complications, arm edema and restriction of shoulder movement and late skin reactions were analyzed. Of the 206 patients 92% showed an excellent to good cosmetic score before radiation therapy. The score deteriorated, but gradually improved and stabilized after 1 year. Eighty-one percent of the patients had an excellent to good cosmetic score at 3 years. The BRA of the 206 patients was 1.8 cm on average before radiation therapy. It increased to 2.3 cm after termination of radiation therapy, and did not change thereafter. Tumor size over 2 cm (p=0.005) and tumors in the inner quadrant (p=0.003) were factors which negatively affected the cosmetic score at 3 years. Tumor size over 2 cm (p=0.003), tumors in the upper quadrant (p=0.005), or a nipple-tumor distance of more than 2 cm (p=0.01) were also negative factors for the BRA at 3 years. Arm edema, restriction of shoulder movement, and late skin reaction were generally mild, and were observed in 12%, 0% and 34% of patients at 3 years, respectively. The overall cosmetic results of breast conserving therapy are acceptable and the complication rate is low. Tumor characteristics, tumor size, location and nipple-tumor distance are factors that affect cosmesis. [ABSTRACT FROM AUTHOR]

Systemic chemotherapy has been increasingly used in the primary treatment of intracranial germinoma. However, the recurrence rate seems to be very high after treatment with chemotherapy alone. We used radiation to treat 5 patients harboring intracranial germinoma that recurred following primary chemotherapy. They had received systemic chemotherapy (4 with cisplatin plus etoposide and 1 with adriamycin, vincristine, cyclophosphamide, prednisolone, and cisplatin) 7–24 months before referral. All patients were treated with conventional radiotherapy directed to the primary tumor site or the craniospinal axis with a dose to the primary site ranging from 39.6 to 47.0 Gy (mean, 42.6 Gy). Response to radiation of all the recurrent tumors was good and all tumors disappeared on diagnostic imaging below the dose of 24 Gy. All patients are alive without further recurrence at 61–129 months after salvage radiotherapy. Germinomas recurring after primary chemotherapy do not seem to have acquired cross resistance to radiotherapy. They can usually be cured by standard radiation therapy with 40–47 Gy. [ABSTRACT FROM AUTHOR]

A rare case of primary large cell carcinoma of the submandibular gland is reported. A 53-year-old man presented with a tumor in the left submandibular region extending to the supraclavicular fossa. After unsuccessful radiochemotherapy at another hospital, he was referred to our department for combined therapy of radiation, hyperthermia, and intraarterial anticancer drug infusion. Although the local tumor decreased in size after therapy, the patient died of respiratory insufficiency due to rapid progression of pulmonary metastases. Autopsy showed that tumor cells in both the submandibular gland and the lung were compatible with undifferentiated large cell carcinoma without tubular formation or laminar structure. The submandibular tumor was considered to be the primary site because cicatricial tissue surrounding the lesion suggested that had formed over a long period. The pulmonary lesions were considered to be metastases because necrosis and intravascular carcinoma cell embolism were noted. The above findings led to the final diagnosis of primary large cell carcinoma of the submandibular gland with pulmonary metastases. This condition has rarely been reported in the literature. [ABSTRACT FROM AUTHOR]

Breast conserving therapy ( BCT) is defined as a combination of conservative surgery for resection of the primary tumor, followed by radiation therapy ( RT) for the eradication of residual microscopic disease in the breast. At NIH Consensus Development Conference in 1990, BCT was recognized as the preferred treatment for the majority of women with Stage I and II breast cancer. RT is a potent loco-regional treament and its role in BCT in reducing local recurrence is already established. On the other hand, the influence of RT on survival outcome has not yet been closely demonstrated so far. RT appears to be useful as neoadjuvant therapy, and also as exclusive local treatment for patients achieving complete regression ( CR) after neoadjuvant chemotherapy. The other possible role of RT is to use it as an alternative to axillary dissection in patients with clinically uninvolved nodes. The question of the appropriateness of using RT in all BCT cases is raised. Since the subgroup of patients who would not deserve any benefit by RT has not yet identified, RT should be delivered as standard treatment following breast conserving surgery for early stage breast cancer. [ABSTRACT FROM AUTHOR]

We report a case of a 28-year-old woman with right-sided breast cancer. The patient had been treated for atopic dermatitis since her infancy. She underwent breast-conserving surgery (BCS) in July 1998, and three titanium clips were placed at the margin of the excision cavity at the time of surgery. Two months after surgery, the patient exhibited a rapid exacerbation of atopic dermatitis. Various drugs were suspected to be the cause of the allergic reaction, but the results of a bi-digital O-ring test (BDORT) suggested an allergic reaction to titanium clips. In August 1999, the patient underwent a second operation to remove the titanium clips under local anesthesia. Allergy to surgical titanium clips is a rare complication, but in patients with a history of severe allergic diseases, a preoperative immunologic examination should be performed and the patient’s history of metal allergy should be investigated. [ABSTRACT FROM AUTHOR]

An abstract to the article "Clinical Trial of Intraoperative Radiation and External-Beam Radiation Combined With Twice-Weekly Gemcitabine for the Treatment of Locally Advanced Pancreatic Cancer," by Michihiko Wada, Ryo Hosotani, Tatehiro Kajiwara, Masaki Kokubo and Michio Senda is presented.