Risk of secondary malignancy after radiotherapy for breast cancer: long-term follow-up of Japanese patients with breast cancer.

PURPOSE: There have been very few reports of secondary malignancies after breast cancer treatment in Asia, particularly in Japan. This study aimed to evaluate the risk of secondary malignancies after radiotherapy (RT) in Japanese breast cancer patients. METHODS: This single-center retrospective study included patients who underwent RT between July 1961 and September 2006 for postoperative breast cancer. A total of 702 patients with a follow-up period of more than 5 years were analyzed. All malignancies observed at more than 5 years after the start of RT were defined as secondary malignancies. To calculate the relative risk (RR) of secondary malignancies, we applied data from the National Cancer Center in Japan. RESULTS: The median observation period was 9.7 (interquartile range 7.1-18.2) years. The cumulative person-years of observation were 6879.4. The RR of contralateral breast cancer increased by 1.85-fold (95% confidence interval [CI] 1.05-3.26) among patients compared with that among the general population; however, the difference was not significant (p = 0.053). The RR of secondary malignancies other than breast cancer increased by 2.71-fold (95% CI 1.99-3.70, p < 0.001) among the patients compared with the general population. Even when only malignancies detected more than 10 years after RT were defined as secondary malignancies, the RR of secondary malignancies other than breast cancer was 1.91 (95% CI 1.33-2.73, p < 0.001). CONCLUSION: The incidence of secondary malignancies after RT may be somewhat higher in Japanese patients with breast cancer than in the general population.

Long-term outcomes of octogenarian pancreatic cancer patients treated with carbon ion radiotherapy.

BACKGROUND: Pancreatic cancer is a disease of the elderly; patients >65 years are 60% of the cases. Due to multiple comorbidities, treating these patients is challenging. We report the efficacy and safety of carbon ion radiotherapy (C-ion RT) in octogenarians. METHODS: We retrospectively analyzed the cases of 46 pancreatic cancer patients aged ≥80 years (median 83, range 80-97) treated with definitive C-ion RT in 2007-2018 at our institute. RESULTS: Twenty-five patients (54%) had resectable or borderline-resectable disease; none underwent surgery (because of medical reasons, e.g., age, multiple comorbidities). C-ion RT was delivered with a median dose of 55.2 Gy (RBE) in 12 fractions. The survivors' median follow-up period was 43 (range 19-76) months. The entire cohort's median overall survival (OS) was 15 (95%CI: 14-22) months with a 3-year OS of 20% (95%CI: 11%-35%). On both univariate and multivariate analyses, baseline CA19-9 remained the significant independent OS prognostic factor (p = 0.032). The 3-year local control rate for all patients was 34% (95%CI: 19%-53%). Local failure (n = 25, 54%) was as common as distant relapse (n = 26, 57%); 33% of the patients experienced both local and systemic failure. About 15% underwent re-C-ion RT for infield recurrence; they achieved a median 22-month OS. No patients exhibited grade ≥3 severe acute or late toxicities (including those who received re-C-ion RT). CONCLUSIONS: C-ion RT in octogenarians with pancreatic cancer showed promising outcomes with acceptable acute and late toxicities and can be considered a reasonable alternative to radical surgery.

Risk of subsequent primary cancers after carbon ion radiotherapy, photon radiotherapy, or surgery for localised prostate cancer: a propensity score-weighted, retrospective, cohort study.

BACKGROUND: The risk of subsequent primary cancers in patients with prostate cancer after treatment with photon radiotherapy is small in absolute numbers, but it is higher than that after surgical treatment. Carbon ion radiotherapy has a theoretically lower risk of inducing secondary malignancies than photon radiotherapy, but this risk has not been investigated in practice because of the low number of facilities offering such therapy worldwide and the limited data on long-term follow-up because the therapy has only been available since 1994. We aimed to analyse the risk of subsequent primary cancers after treatment with carbon ion radiotherapy in patients with localised prostate cancer and to compare it with that after photon radiotherapy or surgery in this setting. METHODS: In this retrospective cohort study, we reviewed records of patients who received carbon ion radiotherapy for prostate cancer between June 27, 1995, and July 10, 2012, at the National Institute of Radiological Sciences (NIRS) in Japan. We also retrieved the records of patients diagnosed and treated for prostate cancer between Jan 1, 1994, and Dec 31, 2012, from the Osaka Cancer Registry. Eligible patients had histologically confirmed localised prostate cancer and a minimum follow-up of at least 3 months; no age restrictions were applied. We excluded patients with metastasis, node-positive disease, or locally invasive (T4 stage) prostate cancer, those with previous or synchronous malignancies, and those who received previous radiotherapy or chemotherapy. We did a multivariable analysis to estimate predictors of subsequent cancers after carbon ion radiotherapy treatment. We also used propensity score inverse probability weighting to retrospectively compare the incidence of subsequent cancers in patients with localised prostate cancer treated with carbon beams, photon radiotherapy, or surgery. FINDINGS: Of 1580 patients who received carbon radiotherapy for prostate cancer at the NIRS, 1455 (92%) patients met the eligibility criteria. Of 38 594 patients with prostate cancer identified in the Osaka registry, 1983 (5%) patients treated with photon radiotherapy and 5948 (15%) treated with surgery were included. Median follow-up durations were 7·9 years (IQR 5·9-10·0) for patients who received carbon ion radiotherapy (after limiting the database to 10-year maximum follow-up), 5·7 years (4·5-6·4) for patients who received photon radiotherapy, and 6·0 years (5·0-8·6) for those who received surgery. 234 subsequent primary cancers were diagnosed in the carbon ion radiotherapy cohort; some patients developed several tumours. On multivariable analysis, age (p=0·0021 for 71-75 years vs ≤60 years; p=0·012 for >75 years vs ≤60 years) and smoking (p=0·0005) were associated with a higher risk of subsequent primary cancers in patients treated with carbon ion radiotherapy. In the propensity score-weighted analyses, carbon ion radiotherapy was associated with a lower risk of subsequent primary cancers than photon radiotherapy (hazard ratio [HR] 0·81 [95% CI 0·66-0·99]; p=0·038) or surgery (HR 0·80 [0·68-0·95]; p=0·0088), whereas photon radiotherapy was associated with a higher risk of subsequent primary cancers than surgery (HR 1·18 [1·02-1·36]; p=0·029). INTERPRETATION: Our analysis suggests that patients with localised prostate cancer treated with carbon ion radiotherapy appear to have a lower risk of subsequent primary cancers than those treated with photon radiotherapy. Although prospective evaluation with longer follow-up is warranted to support these results, our data supports a wider adoption of carbon ion radiotherapy for patients with expected long-term overall survival or those with poor outcomes after receiving conventional treatments. FUNDING: Research Project for Heavy Ions at the National Institute of Radiological Sciences (Japan).

A Unique Case of Intracranial Amelanotic Melanoma with BRAF V600E Mutation Successfully Treated via Molecular-targeted Therapy.

Melanoma carries a high risk of brain metastasis. A small subset of metastatic melanomas, known as amelanotic melanomas, does not present black coloration, reflecting a lack of melanin pigmentation. Here, we report a case of B-Raf proto-oncogene (BRAF) V600E mutation associated with a metastatic brain tumor caused by the amelanotic melanoma. A 60-year-old man was transferred to our department following acute onsets of left upper limb paralysis and convulsion. In the brain imaging, multiple lesions in the right frontal lobe and left basal ganglia were detected, and the presence of an enlarged left axillary lymph node was revealed. Consequently, we removed the right frontal lesion and performed a biopsy of the left axillary lymph node. Histological analysis of both specimens indicated an amelanotic melanoma, and genetic testing revealed a BRAF V600E mutation. The residual intracranial lesions were treated with stereotactic radiotherapy and molecular-targeted therapy, with dabrafenib and trametinib as the systemic treatment. Based on the Response Evaluation Criteria in Solid Tumors, we determined that the patient achieved complete remission (CR) under uninterrupted molecular-targeted therapy over a period of 10 months. After the temporary withdrawal of dabrafenib and trametinib to avoid hepatic dysfunction, a new intracranial lesion appeared. CR of this lesion was achieved following reinstatement of the two drugs. These results suggest that, under limited conditions, molecular-targeted therapy can produce a sustained response against the intracranial metastasis of melanoma, and the therapy with reduced dose is still effective against a recurrent case after cessation of the therapy due to the toxicity.

Secondary cancers after carbon-ion radiotherapy and photon beam radiotherapy for uterine cervical cancer: A comparative study.

BACKGROUND: There are limited studies on the risk of secondary cancers after carbon-ion radiotherapy (CIRT). We assessed the incidence of secondary cancers in patients treated with CIRT for cervical cancer. We also evaluated the incidence of secondary cancers in patients who received standard photon radiotherapy (RT) throughout the same period. METHODS: This retrospective study included patients with cervical cancer who underwent curative RT at our hospital. All cancers discovered for the first time after RT were classified as secondary cancers. To compare the risk of secondary cancers among cervical cancer survivors to the general population, standardized incidence ratios (SIRs) were calculated. RESULTS: The analysis included a total of 197 and 417 patients in the CIRT and photon RT groups, respectively. The total person-years during the observation period were 1052.4 in the CIRT group and 2481.5 in the photon RT group. The SIR for all secondary cancers was 1.1 (95% confidence interval [CI], 0.6-2.1) in the CIRT group and 1.4 (95% CI, 1.0-2.1) in the photon RT group. The 10-year cumulative incidence of all secondary cancers was 9.5% (95% CI, 4.0-21.5) in the CIRT group and 9.4% (95% CI, 6.2-14.1) in the photon RT group. The CIRT and photon RT groups were not significantly different in incidence (p = 0.268). CONCLUSIONS: The incidence of secondary cancers after CIRT for cervical cancer was similar to that after photon RT. Validation of our findings after long-term observation is warranted.

Emergency upper gastrointestinal endoscopy performed safely in a patient with COVID-19 with suspected hemorrhagic shock.

Coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 has spread explosively throughout the world and has since been declared a pandemic by the World Health Organization. Although it is recommended that upper gastrointestinal endoscopies either be postponed or canceled during the pandemic because of their high risk of aerosol generation, this does not apply in emergency cases, which may include patients with coronavirus disease. In this case report, we describe the safe undertaking of an emergency upper gastrointestinal endoscopy in a patient with suspected hemorrhagic shock who tested positive for the severe acute respiratory syndrome coronavirus 2 using the polymerase chain reaction. We performed the procedure in the contamination zone of a specialized coronavirus disease ward with prespecified zones. Full personal protective equipment was worn during the procedure, as recommended by various academic societies, and careful attention was paid to the sterilization of all equipment after the procedure. Thus, emergency endoscopies can be performed safely in patients with coronavirus disease in a suitable environment by using appropriate personal protective equipment and by handling the equipment appropriately.

Real-Time Probing of an Atmospheric Photochemical Reaction by Ultrashort Extreme Ultraviolet Pulses: Nitrous Acid Release from o-Nitrophenol.

Photolysis of o-nitrophenol, contained in brown carbon, is considered to be a major process for the generation of nitrous acid (HONO) in the atmosphere. In this Letter, we used time-resolved photoelectron spectroscopy with 29.5 eV probe pulses and ab initio calculations to disentangle all reaction steps from the excitation to the dissociation of HONO. After excitation, intersystem crossing to the triplet manifold follows ultrafast excited-state intramolecular hydrogen transfer, where the molecules deplanarizes and finally splits off HONO after 0.5-1 ps.

Carbon ion radiotherapy for inoperable pediatric osteosarcoma.

BACKGROUND: Unresectable pediatric osteosarcoma has poor outcomes with conventional treatments. RESULTS: Twenty-six patients aged 11-20 years (median 16) had inoperable osteosarcoma of the trunk (24 pelvic, 1 mediastinal and 1 paravertebral) without any other lesion at initial examination. There were 22 primary, 1 locally recurrent and 3 metastatic cases. Median CIRT dose was 70.4 Gy RBE (relative biological effectiveness) delivered in 16 fractions. Median follow-up was 32.7 months. Overall survival was 50.0% and 41.7% at 3 and 5 years, respectively. Ten patients survived for more than 5 years (range 5-20.7 years). Local control was 69.9% and 62.9% at 3 and 5 years, respectively and progression-free survival was 34.6% at 3 and 5 years. Only largest tumor diameter correlated with 5-year overall survival and local control. There were 4 grade 3-4 CIRT-related late toxicities, 1 case of bone fracture and no treatment-related mortalities. All patients (except 1) were able to ambulate after CIRT. CONCLUSIONS: CIRT was safe and efficacious in the treatment of inoperable pediatric osteosarcoma with improved local control and overall survival compared to conventional treatments. METHODS: We retrospectively reviewed the records of pediatric and adolescent patients who received carbon ion radiotherapy (CIRT) for inoperable osteosarcoma between 1996 and 2014.