Ken Yoshida

Frequency, outcome and prognostic factors of carotid blowout syndrome after hypofractionated re-irradiation of head and neck cancer using CyberKnife: A multi-institutional study

PURPOSE Re-irradiation has attracted attention as a potential therapy for recurrent head and neck tumors. However, carotid blowout syndrome (CBS) has become a serious complication of re-irradiation because of the associated life-threatening toxicity. Determining of the characteristics of CBS is important. We conducted a multi-institutional study. METHODS AND PATIENTS Head and neck carcinoma patients (n=381) were treated with 484 re-irradiation sessions at 7 Japanese CyberKnife institutions between 2000 and 2010. RESULTS Of these, 32 (8.4%) developed CBS, which proved fatal that median survival time after CBS onset was 0.1 month, and the 1-year survival rate was 37.5%. The median duration between re-irradiation and CBS onset was 5 months (range, 0-69 months). Elder age, skin invasion, and necrosis/infection were identified as statistically significant risk factors after CBS by univariate analysis. The presence of skin invasion at the time of treatment found only in postoperative case, is identified as only statistically significant prognostic factor after CBS in multivariate analysis. The 1-year survival rate for the group without skin invasion was 42%, whereas no patient with skin invasion survived more than 4 months (0% at 1 year, p=0.0049). CONCLUSIONS Careful attention should be paid to the occurrence of CBS if the tumor is located adjacent to the carotid artery. The presence of skin invasion at CBS onset is ominous sign of lethal consequences.

New ambulatory implant technique of high-dose-rate interstitial brachytherapy for prostate cancer

PurposeThe aim of this study was to improve the performance status of prostate cancer patients during high-dose-rate interstitial brachytherapy (HDR-ISBT). To this end, we have developed a new ambulatory implant technique.Materials and methodsTen prostate cancer patients were treated with HDR-ISBT as monotherapy from October 2003 until March 2004. We utilized a new removable template, a flexible applicator with a nonmetallic bead and button stopper, and an inner catheter connecting the applicator and the transfer tube of the brachytherapy unit. We shortened the connector end of the flexible applicator to enable the patient to sit down and walk freely during the treatment time.ResultsAll 10 patients could walk without any support. No problem in the application was observed.ConclusionOur new ambulatory implant technique for HDR-ISBT was able to improve the performance status of prostate cancer patients.

High dose rate brachytherapy for oral cancer

Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.

In Vivo Dosimetry of High-Dose-Rate Interstitial Brachytherapy in the Pelvic Region: Use of a Radiophotoluminescence Glass Dosimeter for Measurement of 1004 Points in 66 Patients With Pelvic Malignancy

PURPOSE To perform the largest in vivo dosimetry study for interstitial brachytherapy yet to be undertaken using a new radiophotoluminescence glass dosimeter (RPLGD) in patients with pelvic malignancy and to study the limits of contemporary planning software based on the results. PATIENTS AND METHODS Sixty-six patients with pelvic malignancy were treated with high-dose-rate interstitial brachytherapy, including prostate (n = 26), gynecological (n = 35), and miscellaneous (n = 5). Doses for a total of 1004 points were measured by RPLGDs and calculated with planning software in the following locations: rectum (n = 549), urethra (n = 415), vagina (n = 25), and perineum (n = 15). Compatibility (measured dose/calculated dose) was analyzed according to dosimeter location. RESULTS The compatibility for all dosimeters was 0.98 +/- 0.23, stratified by location: rectum, 0.99 +/- 0.20; urethra, 0.96 +/- 0.26; vagina, 0.91 +/- 0.08; and perineum, 1.25 +/- 0.32. CONCLUSIONS Deviations between measured and calculated doses for the rectum and urethra were greater than 20%, which is attributable to the independent movements of these organs and the applicators. Missing corrections for inhomogeneity are responsible for the 9% negative shift near the vaginal cylinder (specific gravity = 1.24), whereas neglect of transit dose contributes to the 25% positive shift in the perineal dose. Dose deviation of >20% for nontarget organs should be taken into account in the planning process. Further development of planning software and a real-time dosimetry system are necessary to use the current findings and to achieve adaptive dose delivery.

Carotid blowout syndrome in pharyngeal cancer patients treated by hypofractionated stereotactic re-irradiation using CyberKnife: A multi-institutional matched-cohort analysis

BACKGROUND AND PURPOSE Although reirradiation has attracted attention as a potential therapy for recurrent head and neck tumors with the advent of modern radiotherapy, severe rate toxicity such as carotid blowout syndrome (CBOS) limits its potential. The aim of this study was to identify the risk factors of CBOS after hypofractionated stereotactic radiotherapy (SBRT). METHODS AND PATIENTS We conducted a matched-pair design examination of pharyngeal cancer patients treated by CyberKnife reirradiation in four institutes. Twelve cases with CBOS were observed per 60 cases without CBOS cases. Prognostic factors for CBOS were analyzed and a risk classification model was constructed. RESULTS The median prescribed radiation dose was 30 Gy in 5 fractions with CyberKnife SBRT after 60 Gy/30 fractions of previous radiotherapy. The median duration between reirradiation and CBOS onset was 5 months (range, 0-69 months). CBOS cases showed a median survival time of 5.5 months compared to 22.8 months for non-CBOS cases (1-year survival rate, 36% vs.72%; p=0.003). Univariate analysis identified an angle of carotid invasion of >180°, the presence of ulceration, planning treatment volume, and irradiation to lymph node areas as statistically significant predisposing factors for CBOS. Only patients with carotid invasion of >180° developed CBOS (12/50, 24%), whereas no patient with tumor involvement less than a half semicircle around the carotid artery developed CBOS (0/22, 0%, p=0.03). Multivariate Cox hazard model analysis revealed that the presence of ulceration and irradiation to lymph nodes were statistically significant predisposing factors. Thus, we constructed a CBOS risk classification system: CBOS index=(summation of risk factors; carotid invasion >180°, presence of ulceration, lymph node area irradiation). This system sufficiently separated the risk groups. CONCLUSION The presence of ulceration and lymph node irradiation are risk factors of CBOS. The CBOS index, including carotid invasion of >180°, is useful in classifying the risk factors and determining the indications for reirradiation.

High-dose-rate brachytherapy as monotherapy for prostate cancer: technique, rationale and perspective

High-dose-rate (HDR) brachytherapy as monotherapy is a comparatively new brachytherapy procedure for prostate cancer. Although clinical results are not yet mature enough, it is a highly promising approach in terms of potential benefits for both radiation physics and radiobiology. In this article, we describe our technique for monotherapeutic HDR prostate brachytherapy, as well as the rationale and theoretical background, with educational intent.

Transitioning from conventional radiotherapy to intensity-modulated radiotherapy for localized prostate cancer: changing focus from rectal bleeding to detailed quality of life analysis

With the advent of modern radiation techniques, we have been able to deliver a higher prescribed radiotherapy dose for localized prostate cancer without severe adverse reactions. We reviewed and analyzed the change of toxicity profiles of external beam radiation therapy (EBRT) from the literature. Late rectal bleeding is the main adverse effect, and an incidence of >20% of Grade ≥2 adverse events was reported for 2D conventional radiotherapy of up to 70 Gy. 3D conformal radiation therapy (3D-CRT) was found to reduce the incidence to ∼10%. Furthermore, intensity-modulated radiation therapy (IMRT) reduced it further to a few percentage points. However, simultaneously, urological toxicities were enhanced by dose escalation using highly precise external radiotherapy. We should pay more attention to detailed quality of life (QOL) analysis, not only with respect to rectal bleeding but also other specific symptoms (such as urinary incontinence and impotence), for two reasons: (i) because of the increasing number of patients aged >80 years, and (ii) because of improved survival with elevated doses of radiotherapy and/or hormonal therapy; age is an important prognostic factor not only for prostate-specific antigen (PSA) control but also for adverse reactions. Those factors shift the main focus of treatment purpose from survival and avoidance of PSA failure to maintaining good QOL, particularly in older patients. In conclusion, the focus of toxicity analysis after radiotherapy for prostate cancer patients is changing from rectal bleeding to total elaborate quality of life assessment.

Monotherapeutic high-dose-rate brachytherapy for prostate cancer: A dose reduction trial

PURPOSE To report preliminary results of our second regimen with 45.5 Gy/7 fractions aiming to reduce toxicity, compared with our first regimen with 54 Gy/9 fractions, using high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer. MATERIALS AND METHODS From 2005 through 2010, 63 patients with localized prostate cancer were treated with HDR brachytherapy alone in 45.5 Gy/7 fractions for 4 days. Thirty-four patients were considered as intermediate-risk and 29 as high-risk. Thirty-seven patients also received neoadjuvant and/or adjuvant hormonal therapy. Biologically effective dose assuming α/β=1.5 Gy (BED₁.₅) was reduced from 270 Gy to 243 Gy, and BED₃.₀ from 162 Gy to 144 Gy, compared to previous 54 Gy/9 fractions for 5 days. RESULTS Median follow-up time was 42 months (range 13-72). Grade 2 acute toxicities occurred in six (9.5%), late toxicities in five (7.9%) patients, and Grade 3 or higher in none. Grade 2 late gastrointestinal toxicity rate was 1.6%, compared with 7.1% for the 54 Gy regimen. Three-year PSA failure-free rates for intermediate- and high-risk patients were 96% and 90%, which were comparable to 93% and 85% for the 54 Gy regimen. CONCLUSIONS Compared to the 54 Gy/9 fractions regimen, dose-reduced regimen of 45.5 Gy/7 fractions using HDR brachytherapy as monotherapy preliminarily showed an equivalent or lower incidence rate for acute and late toxicities without compromising the excellent PSA failure-free rate. Further studies with more patients and longer follow-up are warranted.

Longitudinal practical measurement of skin color and moisture during and after breast-conserving therapy: influence of neoadjuvant systemic therapy

PurposeThe aim of this study was to assess radiation dermatitis, especially exploring the influence of neoadjuvant systemic therapy (NST).Materials and methodsWe examined maximum toxicity using the Common Toxicity Criteria version 3 score (CTC v3) following radiotherapy between 40 patients treated with NST and 59 patients without NST. In addition, objective skin color (L*, a*, b* values) and moisture analyses were applied in 13 NST and 25 control patients, and the ratio of the values for the irradiated side to the nonirradiated side was calculated.ResultsFor the CTC v3 assessment, 27 grade 1 (68%) and 13 grade 2 (32%) reactions occurred in the NST group and 44 grade 1 (75%) and 15 grade 2 (25%) reactions in the control group. All ratios except the b* ratio showed significant alterations when radiotherapy was added. The ratio of the a* value peaked at the completion of radiotherapy, whereas the L* ratio bottomed out 1 month later. Furthermore, moisture change remained even 1 year after treatment. Boost irradiation doses caused enhanced alterations in the L* and a* ratios. Furthermore, the L* and a* ratios had good agreement with the CTC v3 assessment. NST did not enhance alterations.ConclusionObjective analysis is useful for detailed assessment of radiation dermatitis. NST did not worsen skin reactions.

Preliminary results of MRI-assisted high-dose-rate interstitial brachytherapy for uterine cervical cancer

PURPOSE To investigate the effectiveness of our novel MRI-assisted high-dose-rate interstitial brachytherapy for uterine cervical cancer. METHODS AND MATERIALS Between June 2005 and June 2009, 29 previously untreated patients with cervical cancer were enrolled (2 T2b, 2 T3a, 19 T3b, and 6 T4 tumors). We implanted MRI-compatible plastic catheters using our unique ambulatory technique. The total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy. RESULTS The median D90 (high-risk clinical target volume), D(2 cc) (bladder), and D(2 cc) (rectum) per fraction were 6.9, 5, and 4.6 Gy, respectively. The 3-year local control rates were 100%, 95%, and 83% for T2, T3, and T4 tumors, respectively. Grade 3 or 4 late complications occurred in 4 patients. CONCLUSIONS Our preliminary evaluation of image-based high-dose-rate interstitial brachytherapy showed favorable local treatment results with an acceptable complication rate.