Unresectable bulky chest wall recurrent breast cancer controlled with CT-guided interstitial high-dose-rate brachytherapy and external beam radiotherapy with adjuvant hormonal therapy - case report.

PURPOSE: Bulky chest wall recurrence after mastectomy presents a therapeutic challenge because of high-dose of radiation required to control the disease, and its proximity to low-tolerance organs at risk. We report a case of successful computed tomography (CT)-guided high-dose-rate (HDR) salvage interstitial brachytherapy (ISBT) boost. MATERIAL AND METHODS: A 70-year-old female initially presented with a tumor in right breast, and was treated with mastectomy and adjuvant chemotherapy, followed by hormonal therapy for 5 years without adjuvant radiotherapy. In 2018, 20 years after the initial treatment, she developed unresectable chest wall recurrence that measured 10.5 cm × 7.3 cm × 4.5 cm, with bone and parietal pleura invasion. Biopsy revealed invasive pleomorphic lobular carcinoma [estrogen receptor (ER)-positive, progesterone receptor (PR)-negative, HER2-negative]. There was no evidence of metastatic disease. RESULTS: The patient underwent external beam radiotherapy (EBRT) plus ISBT. After EBRT of 50 Gy in 25 fractions was completed, CT-guided ISBT was performed as an outpatient treatment. HDR dose was 16 Gy delivered in 2 fractions with 2 implants. Dose was prescribed to gross tumor volume. ISBT plans were created using inverse planning simulated annealing (IPSA) algorithm. Gross tumor volume D90% plus EBRT dose was 82 Gy equivalent dose of 2 Gy (EQD2), assuming α/ß of 4 for breast carcinoma. The patient continued on hormonal therapy. At the 30-month follow-up, the patient remains in remission. The tumor could not be detected by magnetic resonance imaging (MRI) or positron emission tomography (PET). There were no severe treatment-related complications. CONCLUSIONS: CT-guided HDR ISBT boost can be a useful modality in individualizing treatment strategies for breast cancer patients with unresectable bulky chest wall recurrence.

Dosimetric predictors of nephrotoxicity in patients receiving extended-field radiation therapy for gynecologic cancer.

PURPOSE: We sought dosimetric predictors of a decreasing estimated glomerular filtration rate (eGFR) in gynecological oncology patients receiving extended-field radiation therapy (EFRT). MATERIALS AND METHODS: Between July 2012 and April 2020, 98 consecutive cervical or endometrial cancer patients underwent EFRT or whole-pelvis radiation therapy (WPRT) with concurrent cisplatin chemotherapy in our institution. To explore the effect of concurrent cisplatin chemotherapy on renal function, the renal function of the WPRT patients was examined. Of the 98 patients, 34 cervical or endometrial cancer patients underwent EFRT including extended-field intensity-modulated radiation therapy (EF-IMRT) and 64 cervical cancer patients underwent WPRT with cisplatin. Of the 34 EFRT patients, 32 underwent concurrent cisplatin chemotherapy. Excluding patients exhibiting recurrences within 6 months, 31 EFRT patients were analyzed in terms of the dose-volume kidney histograms (the percentages of kidney volumes receiving 12, 16, 20, and 24 Gy) and the post- to pre-treatment eGFR ratios. We calculated Pearson correlation coefficients between the renal dose volume and the percentage eGFR reductions of the 31 EFRT patients, and those treated via EF-IMRT. Renal dose constraint significance was evaluated using the Mann-Whitney U test. RESULTS: The eGFR value after WPRT with cisplatin remained largely unchanged for 12 months, unlike that after EFRT. In EFRT patients, a strong correlation was evident between the KV20Gy dose and the post- to pre-treatment eGFR ratio (correlation coefficients - 0.80 for all patients and - 0.74 for EF-IMRT patients). In EF-IMRT patients, the kidney volume receiving 20 Gy tended to correlate negatively with the eGFR reduction. The Mann-Whitney U test showed that patients with KV20Gy values < 10% retained significantly better renal function than did patients with KV20Gy values > 10% (P = 0.002). CONCLUSIONS: Imposition of a severe kidney dose constraint during EF-IMRT may reduce nephrotic toxicity. Future prospective investigations of kidney-sparing EF-IMRT are required.

Late recurrence of a papillary thyroid carcinoma 37 years after hemithyroidectomy: Solitary, left cervical lymph node metastasis evident on fluorodeoxyglucose positron-emission tomography/computed tomography images revealing nodular uptake.

In patients with well-differentiated papillary thyroid carcinoma (PTC), late recurrence is very rare. It is unusual that 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (PET/CT) shows hypermetabolic lesions in patients with well-differentiated PTC metastases. We demonstrate an exceptional case exhibiting a first relapse 37 years after hemithyroidectomy to treat PTC. Recurrent metastasis of a PTC should be considered as a differential diagnosis even if the elapsed time from the initial treatment is great. A left cervical lymphadenopathy, which exceptionally exhibited a hypermetabolic lesion on PET/CT, should be considered a metastatically well-differentiated PTC.

Evaluation of a new bi-valve vaginal speculum applicator design for gynecologic interstitial brachytherapy.

PURPOSE: We designed a bi-valve vaginal speculum high-dose-rate (HDR) interstitial gynecologic brachytherapy applicator. This allows for both a direct view of the cervix and image-guided brachytherapy applicator placement. The purpose of this study was to assess the validity of the new applicator. MATERIAL AND METHODS: The applicator was designed to have a 25-mm arc, which can be spread transversely to 35-mm wide, with 10 insertion holes; it was produced using a stereolithographic printer with biocompatible Dental SG resin. For resin radiodensity was measured in Hounsfield units (HU) using computed tomography (CT). Comparing the new applicator with a conventional intracavitary applicator, we evaluated the treated volume (including dimensions of 100% isodose volume at the central axis), V100/D90/D98 for a hypothetical cervix (a 2-cm-long and 4-cm-diameter cylinder), and dose points of organs at risk (OARs) (at 25 and 30 mm from the tandem). Based on dose-volume histogram (DVH) analysis of the cervix and dose points of OARs, the range of tolerance for the percent dose difference in the prescription dose was set at 5%. RESULTS: The mean radiodensity of the Dental SG resin, which was magnetic resonance imaging compatible, was 118 HU. Dimensions of the 100% isodose volume measured at the central axis were 4.4 × 6.6 × 7.4 cm for the new applicator and 4.3 × 6.0 × 7.7 cm for the intracavitary applicator. The 100% prescription dose volumes were 110 cc and 113 cc for the new and conventional applicator, respectively. The percent difference in the hypothetical cervix V100, D90, and D98 between the new and intracavitary applicator were within 5%. The percent differences in dose points of OARs at 25 and 30 mm between the new and conventional applicators were within 5%. CONCLUSIONS: Our speculum applicator can reproduce a conventional pear-shaped dose distribution. Our current clinical practice will use this applicator, which can improve the patient's treatment results.

CT-Guided Pelvic Lymph Nodal Brachytherapy.

PURPOSE: This is a report of our initial experience using computed tomography (CT)-guided interstitial high dose rate (HDR) brachytherapy to treat bulky pelvic nodal metastases as a part of definitive radiotherapy. MATERIAL AND METHODS: Between February 2015 and April 2019, 14 cervical/endometrial cancer patients presenting with bulky pelvic node(s) underwent nodal interstitial brachytherapy boost in our institution. In total, 17 nodes were treated. The median maximum diameters of the positive nodes at the time of diagnosis and at the first nodal implant were 25 mm (range: 10-65 mm) and 16 mm (range: 9-51 mm), respectively. Dosimetry data of the lymph nodal target volume and small bowel were collected and compared using the paired-sample t-test. Treatment-related toxicities were classified using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median follow-up time for all patients was 26 months. Local recurrence in pelvic nodes occurred in one patient (7%) after 16 months. One patient experienced grade 3 bladder bleeding, and one patient experienced grade 2 pubic bone fracture. No patient had grade 2 or greater gastrointestinal toxicity. In the dosimetric analysis, the mean nodal brachytherapy D90% in terms of the total equivalent dose of 2 Gy (EQD2) was 65.6 Gyαß10. The mean small bowel dose (SBD)0.1cc and SBD1cc in terms of the total EQD2 were 60.4 and 56.5 Gyαß3, respectively. Nodal D90% was significantly higher in terms of the total EQD2 than the SBD0.1cc (p = 0.003) and SBD1cc (p < 0.001). The Kaplan-Meier 2-year pelvic control estimate was 90%. CONCLUSIONS: CT-guided interstitial HDR pelvic nodal brachytherapy appears to be well tolerated with excellent local control in cervical or endometrial cancer patients with bulky pelvic nodes. This approach may offer a useful therapeutic option for unresected bulky pelvic nodes.

Focal low-dose-rate prostate brachytherapy for low- and intermediate-risk prostate cancer.

PURPOSE: To prospectively investigate the efficacy and feasibility of focal low-dose-rate (LDR) prostate brachytherapy for low- and intermediate-risk prostate cancer. MATERIAL AND METHODS: Between October 2014 and May 2019, nineteen low- and intermediate-risk prostate cancer patients who presented with abnormality on both diffusion-weighted and T2-weighted magnetic resonance imaging (MRI) underwent focal LDR brachytherapy at our institution. Focal gross tumor volume (F-GTV) was delineated on transrectal ultrasound, based on abnormality seen on fused T2-weighted MRI. F-GTV was expanded by 5 mm, as a safety margin, to create focal clinical target volume (F-CTV). Prescribed dose to F-CTV was 145 Gy. Biochemical recurrence (BCR) was determined using Phoenix criterion (prostate specific antigen nadir + 2 ng/ml). Pre- and post-implant dosimetry data were compared using non-parametric Wilcoxon's rank sum test. Treatment-related toxicities were evaluated using common terminology criteria for adverse events. RESULTS: Mean F-CTV D90% was significantly lower in the post-implant evaluation than in intraoperative planning (p = 0.004). On post-implant dosimetry, the mean D90% for F-GTV and mean V100% for the entire prostate were 222 Gy and 35%, respectively. Median follow-up time for all patients was 31 months. BCR occurred in one patient after 23 months. Kaplan-Meier 2-year BCR-free rate was 92.9% (95% confidence interval [CI]: 79.4-100%). No patients had grade 1 or greater gastrointestinal toxicity. Three patients who were taking α-blockers to treat benign prostatic hyperplasia (present before brachytherapy), experienced no treatment-related genitourinary toxicities. Two patients suffered from temporary grade 2 urinary frequency. None of the remaining patients experienced grade 2 or higher genitourinary toxicity. CONCLUSIONS: Focal LDR prostate brachytherapy appears acceptable for MRI-based index tumors, with a low cumulative incidence of BCR. Such brachytherapy might offer a feasible minimally invasive therapeutic option for localized prostate cancer.

A novel urethral sparing technique for high-dose-rate prostate brachytherapy after transurethral resection of the prostate.

PURPOSE: The purpose of this study was to assess retrospectively the variability of the urethral dose optimized using a Foley catheter versus urethral contrast injected using a new modified triple-lumen catheter, in CT-based high-dose-rate (HDR) prostate brachytherapy of posttransurethral resection of prostate (TURP) patients. METHODS AND MATERIALS: At our institution, there were six post-TURP patients with prostate carcinoma between July 2014 and April 2016 who underwent transperineal interstitial HDR brachytherapy (16 needles). A custom modified triple-lumen catheter was placed to inject contrast into the TURP defect. Three-dimensional optimal plans using inverse planning simulated annealing algorithm was generated according to radiation therapy oncology group dose requirements. Alternative plans were retroactively generated for comparison using standard technique based on a Foley catheter as a urethral constraint volume for each patient with the same weighting factors. We compared the dosimetry parameters in each planning using Wilcoxon's ranked sum nonparametric test. RESULTS: The median followup of all patients was 17.5 months. No significant genitourinary or gastrointestinal toxicity was noted using this technique. In the dosimetric analysis, the prostate V100 values and TURP urethral V100 were significantly different between plans with and without the contrast (V100 [mean]: 92.4 [%] vs. 94.4 [%], p = 0.046; TURP UV100 [mean]: 1.4 cc vs. 2.2 cc, p = 0.028). There were no statistical differences in the mean values of planning target volume V150%, V200%, and D90, and each bladder V75 and rectum V75. CONCLUSIONS: Post-TURP HDR brachytherapy with urethral contrast showed significantly more volume effect of the TURP defect than that with a Foley catheter alone. Better visualization of the TURP defect should lead to more accurate urethral sparing administration of HDR brachytherapy which is necessary to prevent urethral complication.

Focal partial salvage low-dose-rate brachytherapy for local recurrent prostate cancer after permanent prostate brachytherapy with a review of the literature.

PURPOSE: To investigate the treatment results for focal partial salvage re-implantation against local recurrence after permanent prostate brachytherapy. MATERIAL AND METHODS: Between January 2010 and September 2015, 12 patients were treated with focal partial salvage re-implantation for local recurrence after low-dose-rate brachytherapy using (125)I seeds. The focal clinical target volume (F-CTV) was delineated on positive biopsy areas in a mapping biopsy, combining the cold spots on the post-implant dosimetry for initial brachytherapy. The F-CTV was expanded by 3 mm to create the planning target volume (PTV) as a margin to compensate for uncertainties in image registration and treatment delivery. The prescribed dose to the PTV was 145 Gy. The characteristics and biochemical disease-free survival (BdFS) rates were analyzed. Genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4. RESULTS: The median prostate-specific antigen (PSA) level at re-implantation was 4.09 ng/ml (range: 2.91-8.24 ng/ml). The median follow-up time was 56 months (range: 6-74 months). The median RD2cc and UD10 were 63 Gy and 159 Gy, respectively. The 4-year BdFS rate was 78%, which included non-responders. Biochemical recurrence occurred in two patients after 7 and 31 months, respectively. The former was treated with hormonal therapy after biochemical failure, and the latter underwent watchful waiting (PSA at the last follow-up of 53 months: 7.3 ng/ml) at the patient's request. No patients had grade 3 GU/GI toxicities or died after salvage re-implantation. CONCLUSIONS: The partial salvage low-dose-rate brachytherapy used to treat local recurrence after permanent prostate brachytherapy is well-tolerated, with high biochemical response rates. This treatment can be not only a method to delay chemical castration but also a curative treatment option in cases of local recurrence of prostate carcinoma after seed implantation.

Kidney-Sparing Methods for Extended-Field Intensity-Modulated Radiotherapy (EF-IMRT) in Cervical Carcinoma Treatment.

Coplanar extended-field intensity-modulated radiation therapy (EF-IMRT) targeting the whole-pelvic and para-aortic lymph nodes in patients with advanced cervical cancer results in impaired creatinine clearance. An improvement in renal function cannot be expected unless low-dose (approximately 10 Gy) kidney exposure is reduced. The dosimetric method should be considered during EF-IMRT planning to further reduce low-dose exposure to the kidneys. To assess the usefulness of non-coplanar EF-IMRT with kidney-avoiding beams to spare the kidneys during cervical carcinoma treatment in dosimetric analysis between non-coplanar and coplanar EF-IMRT, we compared the doses of the target organ and organs at risk, including the kidney, in 10 consecutive patients. To estimate the influence of EFRT on renal dysfunction, creatinine clearance values after treatment were also examined in 18 consecutive patients. Of these 18 patients, 10 patients who were included in the dosimetric analysis underwent extended field radiation therapy (EFRT) with concurrent chemotherapy, and eight patients underwent whole-pelvis radiation therapy with concurrent chemotherapy to treat cervical carcinoma between April 2012 and March 2015 at our institution. In the dosimetric analysis, non-coplanar EF-IMRT was effective at reducing low-dose (approximately 10 Gy) exposure to the kidneys, thus maintaining target coverage and sparing other organs at risk, such as the small bowel, rectum, and bladder, compared with coplanar EF-IMRT. Renal function in all 10 patients who underwent EFRT, including coplanar EF-IMRT (with kidney irradiation), was low after treatment, and differed significantly from that of the eight patients who underwent WPRT (no kidney irradiation) 6 months after the first day of treatment (P = 0.005). In conclusion, non-coplanar EF-IMRT should be considered in patients with advanced cervical cancer, particularly in patients with a long life expectancy or with pre-existing renal dysfunction.

Effect of a urinary catheter on seed position and rectal and bladder doses in CT-based post-implant dosimetry for prostate cancer brachytherapy.

PURPOSE: To assess the variability in rectal and bladder dosimetric parameters determined according to post-implant computed tomography (CT) images in patients with or without a urethral catheter. MATERIAL AND METHODS: Patients with prostate cancer who were scheduled to undergo CT after brachytherapy between October 2012 and January 2014 were included. We obtained CT series with and without a urinary catheter in each patient. We compared the rectal and bladder doses in 18 patients on each CT series. RESULTS: The shifts in the seed positions between with and without a catheter in place were 1.3 ± 0.3 mm (mean ± standard deviation). The radiation doses to the rectum, as determined on the CT series, with a urethral catheter were higher than those on CT without a catheter (p < 0.001). Radiation doses to the bladder with a catheter were significantly lower than those without a catheter (p = 0.027). CONCLUSIONS: Post-implant dosimetry (PID) with no catheter showed significantly lower rectal doses and higher bladder doses than those of PID with a catheter. We recommend the PID procedure for CT images in patients without a catheter. Use of CT with a catheter is limited to identifying urethral position.

A new two-step accurate CT-MRI fusion technique for post-implant prostate cancer.

PURPOSE: To develop an accurate method of fusing computed tomography (CT) with magnetic resonance imaging (MRI) for post-implant dosimetry after prostate seed implant brachytherapy. MATERIAL AND METHODS: Prostate cancer patients were scheduled to undergo CT and MRI after brachytherapy. We obtained the three MRI sequences on fat-suppressed T1-weighted imaging (FST1-WI), T2-weighted imaging (T2-WI), and T2*-weighted imaging (T2*-WI) in each patient. We compared the lengths and widths of 450 seed source images in the 10 study patients on CT, FST1-WI, T2-WI, and T2*-WI. After CT-MRI fusion using source positions by the least-squares method, we decided the center of each seed source and measured the distance of these centers between CT and MRI to estimate the fusion accuracy. RESULTS: The measured length and width of the seeds were 6.1 ± 0.5 mm (mean ± standard deviation) and 3.2 ± 0.2 mm on CT, 5.9 ± 0.4 mm, and 2.4 ± 0.2 mm on FST1-WI, 5.5 ± 0.5 mm and 1.8 ± 0.2 mm on T2-WI, and 7.8 ± 1.0 mm and 4.1 ± 0.7 mm on T2*-WI, respectively. The measured source location shifts on CT/FST1-WI and CT/T2-WI after image fusion in the 10 study patients were 0.9 ± 0.4 mm and 1.4 ± 0.2 mm, respectively. The shift on CT/FST1-WI was less than on CT/T2-WI (p = 0.005). CONCLUSIONS: For post-implant dosimetry after prostate seed implant brachytherapy, more accurate fusion of CT and T2-WI is achieved if CT and FST1-WI are fused first using the least-squares method and the center position of each source, followed by fusion of the FST1-WI and T2-WI images. This method is more accurate than direct image fusion.

Prediction of radiosensitivity using phosphorylation of histone H2AX and apoptosis in human tumor cell lines.

PURPOSE: We examined the relationship between radiosensitivity, histone H2AX (γH2AX) phosphorylation, and apoptosis to develop a new predictive assay for radiosensitivity. MATERIALS AND METHODS: Seven human tumor cell lines, including one fibrosarcoma (HT1080), four oesophageal carcinomas (TE-9, KYSE30, KYSE150, and KYSE220), and two breast carcinomas (HCC70, and ZR75-1) were used. Cellular radiosensitivity was assessed using a standard colony-forming assay. To measure the frequency of γH2AX foci, we counted the number of foci per cell under fluorescence microscopy following immunofluorescence staining. DNA content was determined by a flow cytometric assay. To assess the frequency of apoptosis, we enumerated apoptotic cells by fluorescence microscopy 24 hours after irradiation. RESULTS: All seven cell lines showed dose (0-9 Gy)-dependent increases in the number of γH2AX foci per cell 24 h after irradiation. When both the frequency of γH2AX foci normalized by DNA content and the frequency of apoptosis were used, a better correlation was observed between the actual cell survivals and the predicted ones. CONCLUSIONS: Our study shows that the number of γH2AX foci after normalization of the DNA content and apoptotic cell frequency can be used as a new predictive assay for cell survival.

Comparison of hypofractionated and conventionally fractionated whole-breast irradiation for early breast cancer patients: a single-institute study of 1,098 patients.

PURPOSE: To evaluate the efficacy and safety of hypofractionated whole-breast irradiation (HF-WBI) compared with conventionally fractionated (CF) WBI. MATERIALS AND METHODS: Patients with early breast cancer (stages 0-II and <3 positive lymph nodes) who had undergone breast-conserving surgery were eligible for the HF-WBI study. HF-WBI was administered at 43.2 Gy in 16 fractions over 3.2 weeks to the whole breast with an additional tumor-bed boost of 8.1 Gy in 3 fractions over 3 days for positive surgical margins or those <5 mm. CF-WBI was administered at 50 Gy in 25 fractions over 5 weeks to the whole breast with an additional tumor-bed boost of 16 Gy in 8 fractions over 1.4 weeks to 6 Gy in 3 fractions over 3 days, depending on margin status. RESULTS: From April 1, 2006, to December 31, 2010, 717 patients were registered and 734 breasts were treated by HF-WBI. In the same period, 381 patients and 393 breasts who matched the study criteria chose CF-WBI, so the total number of patients in this comparison was 1,098. Grade 2 acute skin reactions were observed for 24 patients (3 %) in the HF-WBI group and 53 patients (14 %) in the CF-WBI (p < 0.001) group. The median follow-up period was 27 months. Two cases of intrabreast tumor recurrence were observed in each treatment group. Regional lymph node recurrence was observed in 1 HF-WBI patient and 2 CF-WBI patients. CONCLUSION: HF-WBI is superior to CF-WBI in terms of acute skin reaction and has the same short-term efficacy.

Radiotherapy with fraction size of 2.25 Gy in T1-2 laryngeal and hypopharyngeal cancer.

This study was carried out to evaluate the influence of fraction size 2.25 Gy on local control of T1 and T2 laryngeal and hypopharyngeal cancers. Between August 2002 and December 2010, 80 patients with T1 and T2 laryngeal or hypopharyngeal cancers were treated with definitive radiotherapy with a fraction size of 2.25 Gy. Primary sites were the larynx in 69 and the hypopharynx in 11. Fifty-three patients were T1 and 27 were T2. All patients' pathology was squamous cell carcinoma except one carcinosarcoma. Radiotherapy was delivered 5 days/week with a 4-MV photon beam up to a total dose of 63.0 Gy. Median treatment time was 41 days. Statistical analysis of survival was calculated using the Kaplan-Meier method. No acute toxicity greater than grade 2 (CTCAE ver. 3.0.) including mucositis and dermatitis was observed. All but one patient had a complete response. The partial response patient received salvage surgery. The median follow-up period was 47 months (ranging from 4 to 108 months). No late toxicity greater than 1 was observed. Nine patients developed recurrence, seven local and two neck lymph nodes. Three patients died, one from laryngeal cancer and two from intercurrent diseases. The 5-year local control rates (LCRs) in the entire group, larynx T1, larynx T2 and hypopharynx T1 were 85.8%, 97.6%, 70.1% and 85.7%, respectively. The LCRs of T1 improved compared with our historical control, but not those of T2. The 2.25-Gy fraction size is safe and may have the potential to achieve good LCR in T1 lesions.