Effective timing of hyaluronate gel injection in image-guided adaptive brachytherapy for uterine cervical cancer: a proposal of the 'adjusted dose score'.

Hyaluronate gel injection (HGI) in the rectovaginal septum and vesicovaginal septum is effective in the setting of high-dose-rate image-guided adaptive brachytherapy (IGABT) for cervical cancer. We aimed to retrospectively investigate optimal conditions for HGI to achieve optimal dose distribution with a minimum number of HGI. We classified 50 IGABT plans of 13 patients with cervical cancer who received IGABT both with and without HGI in the rectovaginal septum and vesicovaginal septum into the following two groups: plan with (number of plans = 32) and plan without (number of plans = 18) HGI. The irradiation dose parameters of high-risk clinical target volume (CTVHR) and organs at risk per fraction were compared between these groups. We also developed the adjusted dose score (ADS), reflecting the overall irradiation dose status for four organs at risk and CTVHR in one IGABT plan and investigated its utility in determining the application of HGI. HGI reduced the maximum dose to the most exposed 2.0 cm3 (D2.0 cm3) of the bladder while increasing the minimum dose covering 90% of CTVHR and the percentage of CTVHR receiving 100% of the prescription dose in one IGABT plan without causing any associated complications. An ADS of ≥2.60 was the optimum cut-off value to decide whether to perform HGI. In conclusion, HGI is a useful procedure for improving target dose distribution while reducing D2.0 cm3 in the bladder in a single IGABT plan. The ADS can serve as a useful indicator for the implementation of HGI.

Dynamics in the expression of programmed death ligand 1 and cluster of differentiation 163 in the tumor microenvironment of uterine cervical cancer: a single-center retrospective study.

BACKGROUND: Radiotherapy (RT) destroys cancer cells and activates the immune system while suppressing the immunity of tumor-associated tissues, including the tumor microenvironment (TME). However, to date, no anti-tumor therapeutic strategy that uses these immune mechanisms has been established. This study investigated changes in the immunity of the TME during standard radical RT for cervical cancer combined with external beam RT and brachytherapy and determined whether these changes affect prognosis. METHODS: Twenty-six patients who had completed radical RT for cervical cancer were categorized into the following two groups according to whether the cancer recurred and/or metastasized within 2 years after the start of treatment: treatment failure (n = 14) and treatment success (n = 12). We assessed the expression of programmed death 1, programmed death ligand 1 (PD-L1), cluster of differentiation (CD) 8, CD68, CD163, Forkhead box protein P3, and hypoxia-inducible factor-1α in the TME of cervical tissues collected periodically during treatment and evaluated the difference in expression rates of each marker between the success and failure groups and assessed its effect on prognosis. RESULTS: The expression levels of PD-L1 and CD163 in the TME in the treatment success group were lower than those in the treatment failure group at the midpoint during brachytherapy (p < 0.01 and p = 0.08, respectively), and the 2-year progression-free-survival (PFS) rate depended on the expression levels of PD-L1 and CD163 (p = 0.04 and p = 0.02, respectively). CONCLUSIONS: The expression rates of CD163 and PD-L1 in the TME during brachytherapy were related to treatment response and the 2-year PFS. This study may increase our understanding of tumor-associated immunity in the TME and aid in the development of therapies targeting PD-L1 or M2 macrophages in the TME in conjunction with RT, especially brachytherapy, for cervical cancer patients.

Hydrogel spacer injection to the meso-sigmoid to protect the sigmoid colon in cervical cancer brachytherapy: A technical report.

Purpose: The use of a hydrogel spacer inserted into recto-vaginal fossa is a valuable strategy to mitigate radiation exposure to the rectum during radiation therapy for female pelvic malignancies. However, when the sigmoid colon is in proximity to the cervix, radiation exposure to the sigmoid colon cannot be adequately mitigated with a hydrogel spacer injected into the recto-vaginal fossa. Here, we presented a case, in which a hydrogel spacer was injected into the meso-sigmoid to protect the sigmoid colon. Material and methods: A 73-year-old female diagnosed with T3b stage IIIC2r uterine cervical cancer (FIGO 2018) underwent high-dose-rate interstitial brachytherapy consisting of 24 Gy in 4 fractions, following concurrent chemoradiotherapy with external beam radiation therapy of 50 Gy in 25 fractions of whole pelvic radiation therapy. In the initial brachytherapy, the sigmoid colon was in close contact with the uterine cervix. In the second brachytherapy, attempts to create a space between the sigmoid colon and uterine cervix using injected artificial ascites were unsuccessful due to rapid absorption of fluid. In the third and fourth brachytherapy fractions, 5 mL of hydrogel was injected into the meso-sigmoid through a pouch of Douglas under trans-rectal ultrasonography guidance. Dose ratio of sigmoid colon D2cc and high-risk clinical target volume (HR-CTV) D90 of each brachytherapy were evaluated. Results: Dose ratio of the sigmoid colon D2cc to HR-CTV D90 was 1.03, 0.43, 0.56, and 0.47 in each respective brachytherapy session, indicating dose escalation to HR-CTV whilst achieving acceptable sigmoid dose with hydrogel spacer injected into the meso-sigmoid. Conclusions: The dose ratio of the sigmoid colon to HR-CTV D90 was decreased by introducing a hydrogel spacer into the meso-sigmoid. In cases where the sigmoid colon is in proximity to the cervical tumor, this novel technique can be considered to achieve better clinical outcomes.

Technical report: a high-dose-rate interstitial brachytherapy boost for residual sinonasal undifferentiated carcinoma.

Sinonasal undifferentiated carcinoma (SNUC) is a highly aggressive and uncommon neoplasm that arises from the mucosa of the nasal cavity or paranasal sinuses. The multidisciplinary approach that includes surgery, radiation therapy (RT), and chemotherapy has been proven to improve survival rates. However, there is no established evidence for the efficacy of further (boost) irradiation following definitive RT in SNUC patients with residual primary tumor. We describe a successful case of a patient with SNUC who had an uncontrolled primary tumor following induction chemotherapy and radical concurrent chemoradiotherapy (CCRT) and underwent a high-dose-rate interstitial brachytherapy (HDR-ISBT) boost. A 75-year-old Japanese woman with unresectable locally advanced SNUC (LA-SNUC) received induction chemotherapy followed by radical CCRT. However, because the residual primary tumor was evident after planned external beam RT, she underwent an HDR-ISBT boost, and the tumor decreased significantly. A complete response (the Response Evaluation Criteria in Solid Tumors, ver. 1.1) was achieved 2 months after brachytherapy, and the patient has been disease-free for 2 years following treatment initiation. In conclusion, an HDR-ISBT boost can be a safe and effective treatment option in patients with residual and inoperable LA-SNUC in the maxillary sinus after initial RT.

Salvage image-guided freehand interstitial brachytherapy for pelvic sidewall recurrence after hysterectomy for uterine malignancies.

PURPOSE: Pelvic sidewall recurrence after hysterectomy for uterine malignances has a poor prognosis, and the salvage therapy for this type of recurrence is still challenging. The purpose of this study was to investigate the efficacy of freehand high-dose-rate interstitial brachytherapy (HDR-ISBT) through the perineum using transrectal ultrasonography for this disease. METHODS AND MATERIALS: We retrospectively evaluated 42 patients with pelvic sidewall recurrence after hysterectomy for uterine cervical and endometrial cancers. We investigated patients' characteristics, the 2-year local control and survival rates, and late adverse events of the rectum and bladder. RESULTS: The 2-year overall survival, local control, and progression-free survival rates were 73.7% (95% confidence interval [CI], 60.8-89.3%), 69.4% (95% CI, 55.4-80.1%), and 37.3% (95% CI, 24.6-56.5%), respectively. In Cox multivariate analysis, tumor size at recurrence (<45 mm vs. ≥45 mm) (p = 0.04) and disease-free periods after hysterectomy (<10 months vs. ≥10 months) (p < 0.01) were significant prognostic factors for overall survival. Lymph node metastasis at recurrence (p < 0.01) was also a significant prognostic factor for progression-free survival. Three patients experienced Grade 3-4 late proctitis (7%). CONCLUSIONS: Transperineal freehand salvage HDR-ISBT using transrectal ultrasonography was demonstrated to be a curative treatment option for patients with pelvic sidewall recurrence following hysterectomy. Based on the findings of this study, we emphasize the importance of HDR-ISBT for pelvic sidewall recurrence.

Comparative Treatment Outcome in T3N0 Glottic Cancer With and Without Vocal Fold Fixation Receiving Radiation Therapy and Concurrent Low-Dose Intra-Arterial Cisplatin Infusion.

OBJECTIVES: Selective radiotherapy and concomitant intra-arterial cisplatin infusion (m-RADPLAT) with a lower cisplatin dosage have been performed for organ and function preservation in patients with locally advanced squamous cell carcinoma of the larynx (SCC-L), and results showing a lower rate of adverse events have been reported. This study evaluated the treatment outcomes of patients with T3N0 glottic SCC-L with or without vocal fold fixation (VFF) who were treated with m-RADPLAT. METHODS: We retrospectively reviewed the data of 33 patients with T3N0 SCC-L who received m-RADPLAT. RESULTS: The vocal fold in patients with VFF 3 months after completing m-RADPLAT resumed normal movement in 15 patients (83%) and persisted fixation in 3 (17%). The 3-year local control, laryngeal cancer-specific survival, and overall survival rates of patients with or without VFF were 88.9% and 86.7%, 94.1% and 93.3%, and 88.9% and 86.7%, respectively. Additionally, the 3-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates of patients with or without VFF were 94.4% and 86.7%, 88.9% and 73.3%, and 83.3% and 73.3%, respectively. Grade 3 or higher toxicities were observed in all patients: leukopenia in 4 patients (12%), neutropenia in 5 (15%), anemia in 2 (6%), thrombocytopenia in 3 (9%), and mucositis in 2 (6%). CONCLUSIONS: This study demonstrated that m-RADPLAT yielded VFF improvement and a favorable survival while maintaining laryngeal function not only in patients with T3N0 glottic SCC-L without VFF but also in patients with VFF.

Radiation-Induced Olfactory Neuroblastoma Following Treatment for NK/T-cell Lymphoma, Nasal Type.

Radiation-induced olfactory neuroblastoma (ONB) is an uncommon neoplasm that is generally associated with a poor prognosis. We experienced an unusual case of ONB in a patient who had received previous radiation therapy for extranodal NK/T-cell lymphoma 15 years previously. To our knowledge, this is the first report of a patient with radiation-induced ONB obtaining a complete response (CR) with radical re-irradiation alone. The purpose of this report is to discuss therapeutic strategies for radiation-induced ONB. We report an unusual case of ONB suspected to be a radiation-induced neoplasm in a 33-year-old female who had received 30 Gy of irradiation for extranodal NK/T-cell lymphoma, nasal type (NTCL) 15 years earlier. In this case, the patient presented with nasal obstruction and frequent epistaxis. The patient was diagnosed with ONB based on left nasal biopsy findings. The surrounding normal tissues tolerance of nasal ONB radiation had to be limited, because the previously radiated NTCL was located adjacent to critical organs. We performed intensity modulated radiation therapy (IMRT), which could offer precise irradiation (60 Gy in 2 Gy daily fractions) while sparing critical tissues. The present case was treated with radiation therapy alone, whereas previously reported cases were treated with a combination of chemotherapy and radiation therapy. We treated radiation-induced OBN successfully with radical re-irradiation using IMRT alone and the patient has had no recurrence for 3 years.

Analysis of radioactive implant migration in patients treated with iodine-125 seeds for permanent prostate brachytherapy with MRI-classified median lobe hyperplasia.

PURPOSE: Prostate cancer with median lobe hyperplasia (MLH) is a relative contraindication for permanent prostate brachytherapy (PPB) because of an increased risk of post-implant dysuria and technical difficulties associated with achieving stability while implanting within the intravesical tissue. We examined treatment outcome, seed migration, and urination disorders after treatment in MLH patients in order to determine to what degree MLH implants could be stabilized. MATERIAL AND METHODS: Between March 2007 and December 2016, 32 patients had MLH identified radiologically on magnetic resonance imaging, and 193 patients did not have MLH (non-MLH). All patients were treated with loose seeds. In this study, seed migration was defined as a seed distant from the target (≥ 1.5 cm) and/or with no dosimetric contribution to the target. The MLH patients were divided into 2 MLH groups of mild (< 10 mm) and severe (≥ 10 mm) MLH by measuring the distance between the posterior transitional zone and the prostatic tissue protruding into the bladder. We retrospectively analyzed seed migration, dose-volume histograms (DVH), and genitourinary toxicity. RESULTS: MLH was classified as mild in 24 patients and severe in 8. Seed migration occurred in 61 (31.6%) of 193 non-MLH patients and 10 (31.5%) of 32 MLH patients. Implant seed migration and low-dose level of median lobe tended to be high in severe MLH cases. International Prostate Symptom Score (IPSS) peaked one month after implantation, but then resolved slowly and returned to around the pre-treatment level after one year. There were no severe complications. CONCLUSIONS: MLH does not appear to be a strong contraindication for low-dose-rate brachytherapy. However, we found that the seed migration and degree of cold spots tended to be higher in severe MLH cases than in others; therefore, close attention when treating severe MLH cases must be paid.

Organ preservation following radiation therapy and concurrent intra-arterial low dose cisplatin infusion for advanced T2 and T3 laryngeal cancer: Long-term clinical results from a pilot study.

BACKGROUND: This pilot study evaluated the long-term outcomes of patients with advanced T2 or T3 squamous cell carcinoma of the larynx (SCC-L) who were treated with selective intra-arterial cisplatin and concomitant radiotherapy (RADPLAT). METHODS: We retrospectively investigated the data of 49 patients with advanced T2 or T3 SCC-L who received a RADPLAT regimen with low-dose cisplatin. RESULTS: The 5-year locoregional control, disease-specific survival, and overall survival rates were 83.3%, 88.1%, and 82.6%, respectively, while the 5-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates were 89.6%, 79.4%, and 77.1%, respectively. The incidences of grade 3-4 hematologic and nonhematologic toxicities were 18% and 6%, respectively. Although two patients (4%) developed late toxicities within 5 years following RADPLAT, no other events were noted beyond 5 years. CONCLUSION: This pilot study demonstrated that RADPLAT is feasible and safe and yielded favorable survival outcomes and functional laryngeal preservation in patients with advanced T2 or T3 SCC-L. LEVEL OF EVIDENCE: 3.