Kenji Sekiguchi

Reevaluation of postoperative radiotherapy for thoracic esophageal carcinoma

PURPOSE To reevaluate postoperative radiotherapy for thoracic esophageal carcinoma. METHODS AND MATERIALS Reviewed were the outcome of 89 patients who underwent esophagectomy with systematic dissection of regional lymph nodes between 1988 and 1993. Of the 89 patients, 19 underwent no adjuvant treatment, 22 underwent adjuvant chemotherapy alone, and 48 underwent postoperative radiotherapy. Twelve of the 48 also underwent adjuvant chemotherapy. RESULTS All patients who experienced local-regional recurrence had lymph node metastases at the time of surgery. The actuarial local-regional control rate at 2-year of follow-up was 94% for patients with lymph node metastases at the time of surgery who underwent postoperative radiotherapy alone or plus chemotherapy, and 74% for those who underwent adjuvant chemotherapy alone. The local-regional control rate was significantly better for those who had undergone postoperative radiotherapy (p < 0.01). CONCLUSIONS Postoperative radiotherapy still plays an important role as adjuvant treatment.

Variability in Bladder Volumes of Full Bladders in Definitive Radiotherapy for Cases of Localized Prostate Cancer

AbstractBackground and Purpose:To evaluate variation in bladder volume of full bladders in definitive radiotherapy for localized prostate cancer and to investigate potential predictors of increased bladder volume variations.Patients and Methods:In 40 patients, the bladder volume was measured with megavoltage computed tomography (MVCT) imaging performed just before irradiation during the administration of the 1st fraction (#1), the 10th fraction (#10), the 20th fraction (#20), and the 30th fraction (#30). Patients were instructed to avoid urinating for 60–90 minutes before the planning CT (pln-CT) scan and before daily irradiation. Patients were also encouraged to drink an unspecified volume of liquid that would result in a clear but tolerable urge to urinate.Results:The population-mean bladder volume (±1SD) was 219 ml (±83 ml) at the planning CT scan (pln-CT), 186 ml (±96 ml) at #1, 149 ml (±73 ml) at #10, 137 ml (±59 ml) at #20, and 136 ml (±60 ml) at #30. The mean intrapatient variation in bladder volume (1 SD relative to the mean bladder volume of each patient) was 38% (range: 10–84%). The bladder volume at the pln-CT was correlated with the intrapatient variance in bladder volume with a correlation coefficient of 0.54 and p <0.001.Conclusion:We observed a significant decline in bladder volumes during the course of radiotherapy. The bladder volume at the pln-CT was a significant predictor of increased bladder volume variations.ZusammenfassungHintergrund und Zweck:Die Evaluierung der Schwankungen des Blasenvolumens gefüllter Blasen in der definitiven Radiotherapie bei lokalisiertem Prostatakrebs sowie die Untersuchung potenzieller Prädiktoren für erhöhte Schwankungen des Blasenvolumens.Patienten und Methoden:Das Blasenvolumen von vierzig Patienten wurde mittels Megavoltage-Computertomographie (MVCT) bestimmt, die bei der Verabreichung der 1. Fraktion (#1), der 10. Fraktion (#10), der 20. Fraktion (#20) und der 30. Fraktion (#30) kurz vor der Bestrahlung durchgeführt wurde. Die Patienten wurden angewiesen, 60–90 Minuten vor dem Planungs-CT (pln-CT)- Scan und vor der täglichen Bestrahlung nicht zu urinieren. Die Patienten wurden zudem ermuntert, eine nicht näher bestimmte Menge an Flüssigkeit zu sich zu nehmen, um einen deutlichen aber tolerierbaren Harndrang herbeizuführen.Ergebnisse:Der Mittelwert der Grundgesamtheit des Blasenvolumens (±1SA) lag beim Planungs-CT-Scan (pln-CT) bei 219 ml (±83 ml), 186 ml (±96 ml) bei #1, 149 ml (±73 ml) bei #10, 137 ml (±59 ml) bei #20 und 136 ml (±60 ml) bei #30. Der Mittelwert der Schwankung des Blasenvolumens innerhalb eines Patienten (1SA bezogen auf den Mittelwert des Blasenvolumens des einzelnen Patienten) lag bei 38 % (Spannweite: 10–84 %). Das Blasenvolumen zum Zeitpunkt des pln-CT wurde mit der Streuung des Blasenvolumens innerhalb eines Patienten korreliert, woraus sich ein Korrelationskoeffizient von 0,54 mit p <0,001 ergab.Fazit:Im Laufe der Radiotherapie konnte eine deutliche Verringerung der Blasenvolumen festgestellt werden. Das Blasenvolumen zum Zeitpunkt des pln-CT-Scans erwies sich als signifikanter Prädiktor erhöhter Schwankungen im Blasenvolumen.

The relationship between the bladder volume and optimal treatment planning in definitive radiotherapy for localized prostate cancer

Abstract Background. There is no current consensus regarding the optimal bladder volumes in definitive radiotherapy for localized prostate cancer. The aim of this study was to clarify the relationship between the bladder volume and optimal treatment planning in radiotherapy for localized prostate cancer. Material and methods. Two hundred and forty-three patients underwent definitive radiotherapy with helical tomotherapy for intermediate- and high-risk localized prostate cancer. The prescribed dose defined as 95% of the planning target volume (PTV) receiving ≧ 100% of the prescription dose was 76 Gy in 38 fractions. The clinical target volume (CTV) was defined as the prostate with a 5-mm margin and 2 cm of the proximal seminal vesicle. The PTV was defined as the CTV with a 5-mm margin. Treatment plans were optimized to satisfy the dose constraints defined by in-house protocols for PTV and organs at risk (rectum wall, bladder wall, sigmoid colon and small intestine). If all dose constraints were satisfied, the plan was defined as an optimal plan (OP). Results. An OP was achieved with 203 patients (84%). Mean bladder volume (± 1 SD) was 266 ml (± 130 ml) among those with an OP and 214 ml (±130 ml) among those without an OP (p = 0.02). Logistic regression analysis also showed that bladder volumes below 150 ml decreased the possibility of achieving an OP. However, the percentage of patients with an OP showed a plateau effect at bladder volumes above 150 ml. Conclusions. Bladder volume is a significant factor affecting OP rates. However, our results suggest that bladder volumes exceeding 150 ml may not help meet planning dose constraints.

Management of locoregional recurrence of breast cancer

The locoregional recurrence of breast cancer is not a sign of distant metastases, and a substantial proportion of cases are cured by salvage therapy. Patients with locoregional recurrence should not be treated with palliative intent as if they have visceral metastases. The recommended treatment for ipsilateral breast recurrence after breast conservative therapy is a mastectomy. For patients who suffer from isolated chest wall recurrence after mastectomy, a surgical approach is recommended. Neoadjuvant chemotherapy is considered for patients with unresectable disease in order to render the disease resectable. For patients with isolated chest wall recurrence who have received no prior radiotherapy, postoperative radiotherapy involving the chest wall and regional lymph nodes is recommended. Patients with isolated axillary lymph node recurrence should be treated with axillary dissection or resection. Although the effectiveness of systemic therapy for patients with locoregional recurrence is unclear, there is a trend toward treating patients with supraclavicular lymph node recurrence with radiotherapy plus systemic therapy. Pain relief and the eradication of other distressing symptoms resulting from inoperable disease are achieved in two-thirds to three-quarters of patients by radiotherapy with or without systemic therapy. New anti-cancer agents and molecular target therapies should be evaluated with the objective of improving the treatment outcome of patients with locoregional recurrence. A combination of approaches is required for treatment of patients with locoregional recurrence, and a multidisciplinary tumor board should be organized at each institute.

Factors influencing survival outcome for radiotherapy for biliary tract cancer: A multicenter retrospective study

PURPOSE To seek for the possible factors influencing overall survival (OS) with radiotherapy (RT) for biliary tract cancer. MATERIALS AND METHODS Data were collected retrospectively from RT database of 31 institutions in Japan. All patients underwent at least external beam RT. The factors influencing OS were investigated. RESULTS Data of 498 patients were analyzed. Median OS of the 212 patients who underwent surgery was significantly better than that of the 286 patients without surgery (31 vs. 15 months, p<0.001). The OS for the R0 or R1 resection group was significantly longer than that for the R2 or non-surgery group, as well as for n0 compared to n1 (all p<0.001). Chemoradiotherapy (CRT), both sequential and concurrent, resulted in a better OS than RT alone for the n1 group (31 vs. 13 months, p<0.001), and marginally better for the R0/R1 group (p=0.065; p=0.054 for concurrent CRT). However, no such benefit was observed for the R2/non-surgical patients. Multivariate analysis identified performance status, clinical stage, and surgery as significant factors. CONCLUSION Surgery, especially R0/R1 resection, seemed as the gold standard for treatment of biliary tract cancer including RT, even in the highly heterogeneous population obtained from the multicenter retrospective study. The possibility was shown that CRT yielded better survival benefit especially for n1 patients. We recommend that future prospective trials include an arm of adjuvant CRT at least for n1 and possibly R0/R1 patients.

Quantification of Cold Spots Caused by Geometrical Uncertainty in Field-in-field Techniques for Whole Breast Radiotherapy

OBJECTIVE To quantify the cold spot under geometrical uncertainties in field-in-field techniques for whole breast radiotherapy. METHODS Ten consecutive patients from both the left- and right-sided treatment site groups who received whole breast radiotherapy with the field-in-field technique were included. Virtual plans were made with moving isocenters to the posterior direction having two amplitudes (5 and 10 mm) and prescribing the same monitor unit as the original plan (FIF_5 and FIF_10). The planning target volume for evaluation was defined by subtracting the areas within 5 mm from the skin and within 5 mm from the lung from the whole breast. The differences in V90, V95 and D98 of planning target volume for evaluation were measured between the original and virtual plans. As a reference, the same measurements were taken for the wedge techniques (Wedge_5 and Wedge_10). RESULTS The differences in V95 were -0.2% on FIF_5, -1.7% on FIF_10, -0.5% on Wedge_5 and -1.5% on Wedge_10. The differences in V90 were -0.02% on FIF_5, -0.3% on FIF_10, -0.05% on Wedge_5 and -0.1% on Wedge_10. The differences in D98 were 0 Gy on FIF_5, -0.1 Gy on FIF_10, -0.2 Gy on Wedge_5 and -0.4 Gy on Wedge_10. The differences in D98 between the original plans and virtual scenarios for field-in-field techniques were significantly smaller than those for wedge techniques, but there were no statically significant differences in V90 and V95. CONCLUSIONS The quantity of the cold spots caused by the geometrical uncertainties in field-in-field techniques was similar to that for the wedge techniques and was acceptable.

Frequency and Clinical Significance of Previously Undetected Incidental Findings Detected on Computed Tomography Simulation Scans for Breast Cancer Patients

PURPOSE To determine the frequency and clinical significance of previously undetected incidental findings found on computed tomography (CT) simulation images for breast cancer patients. METHODS AND MATERIALS All CT simulation images were first interpreted prospectively by radiation oncologists and then double-checked by diagnostic radiologists. The official reports of CT simulation images for 881 consecutive postoperative breast cancer patients from 2009 to 2010 were retrospectively reviewed. Potentially important incidental findings (PIIFs) were defined as any previously undetected benign or malignancy-related findings requiring further medical follow-up or investigation. For all patients in whom a PIIF was detected, we reviewed the clinical records to determine the clinical significance of the PIIF. If the findings from the additional studies prompted by a PIIF required a change in management, the PIIF was also recorded as a clinically important incidental finding (CIIF). RESULTS There were a total of 57 (6%) PIIFs. The 57 patients in whom a PIIF was detected were followed for a median of 17 months (range, 3-26). Six cases of CIIFs (0.7% of total) were detected. Of the six CIIFs, three (50%) cases had not been noted by the radiation oncologist until the diagnostic radiologist detected the finding. On multivariate analysis, previous CT examination was an independent predictor for PIIF (p = 0.04). Patients who had not previously received chest CT examinations within 1 year had a statistically significantly higher risk of PIIF than those who had received CT examinations within 6 months (odds ratio, 3.54; 95% confidence interval, 1.32-9.50; p = 0.01). CONCLUSIONS The rate of incidental findings prompting a change in management was low. However, radiation oncologists appear to have some difficulty in detecting incidental findings that require a change in management. Considering cost, it may be reasonable that routine interpretations are given to those who have not received previous chest CT examinations within 1 year.

Effects of Geometrical Uncertainties on Whole Breast Radiotherapy: A Comparison of Four Different Techniques

Purpose The purpose of this study was to quantify the target coverage, homogeneity, and robustness of the dose distributions against geometrical uncertainties associated with four whole breast radiotherapy techniques. Methods The study was based on the planning-computed tomography-datasets of 20 patients who underwent whole breast radiotherapy. A total of four treatment plans (wedge, field-in-field [FIF], hybrid intensity-modulated radiotherapy [IMRT], and full IMRT) were created for each patient. The hybrid IMRT plans comprised two opposed tangential open beams plus two IMRT beams. Setup errors were simulated by moving the beam isocenters by 5 mm in the anterior or posterior direction. Results With the original plan, the wedge technique yielded a high volume receiving ≥107% of the prescription dose (V107; 7.5%±4.2%), whereas the other three techniques yielded excellent target coverage and homogeneity. A 5 mm anterior displacement caused a large and significant increase in the V107 (+5.2%±4.1%, p<0.01) with the FIF plan, but not with the hybrid IMRT (+0.4%±1.2%, p=0.11) or full IMRT (+0.7%±1.8%, p=0.10) plan. A 5-mm posterior displacement caused a large decrease in the V95 with the hybrid IMRT (-2.5%±3.7%, p<0.01) and full IMRT (-4.3%±5.1%, p<0.01) plans, but not with the FIF plan (+0.1%±0.7%, p=0.74). The decrease in V95 was significantly smaller with the hybrid IMRT plan than with the full IMRT plan (p<0.01). Conclusion The FIF, hybrid IMRT, and full IMRT plans offered excellent target coverage and homogeneity. Hybrid IMRT provided better robustness against geometrical uncertainties than full IMRT, whereas FIF provided comparable robustness to that of hybrid IMRT.

Controversies in the role of postmastectomy radiotherapy in breast cancer patients with one to three positive axillary nodes and safety of integrating radiotherapy and breast reconstruction

In this special feature, readers will find four articles related to postmastectomy radiotherapy (PMRT). In two articles the issue of whether to recommend PMRT to all patients with 1–3 positive nodes was discussed. The use of PMRT has been widely accepted for patients with four or more positive lymph nodes, but controversy has remained regarding the role of PMRT for those with 1–3 positive nodes. In 2014, the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) published an updated meta-analysis of the effects of PMRT [1] which generated renewed interest in the value of PMRT. One of the main findings is that PMRT is not only highly effective at preventing locoregional recurrence (LRR) but also reduces the risk of distant metastases and breast cancer mortality in patients with 1–3 positive nodes. Among 1314 patients with 1–3 positive nodes, PMRT resulted in a 10-year absolute decrease in any first recurrence of 11.5% and a 20-year decrease in breast cancer mortality of 7.9% (both P B 0.01). However, the issue of PMRT for patients with 1–3 positive nodes remains far from being resolved even in light of this meta-analysis. Many clinicians seem to not believe that the favorable outcomes seen in the metaanalysis are generalizable to all breast cancer patients with 1–3 positive nodes. Following the publication of the EBCTCG meta-analysis (June 2014), the consensus panel of the 14th St. Gallen Breast Cancer Conference (March 2015) considered that PMRT should be standard for patients with 1–3 involved nodes and adverse pathology. However, in the absence of adverse pathology, these patients could be treated without PMRT, although a slim majority would include such treatment for patients aged\40 years (51%) [2]. In Japan, the questionnaire distributed at around the same time revealed that PMRT is never delivered to patients with 1–3 positive nodes at 41% of the institutes; PMRT is applied all of the time only in a minority of institutions (7.7%) [3]. It is of course very important to scrutinize the evidence provided through recent studies, even if it is of high quality via a systematic review and meta-analysis. Thus, the debate in this issue by Ishikawa et al. and Tada et al. surrounding the pros and cons of PMRT in the setting of 1–3 positive nodes is both highly attractive and very timely [4, 5]. It should be considered that systemic and radiotherapy standards have improved considerably during the course of many of the studies included in the meta-analysis. Systemic therapy has proved to be highly effective at reducing the risk of both distant relapse and LRR. The trials included in the meta-analysis were predominantly conducted in the 1970s and 1980s and CMF and/or tamoxifen was usually used at that time. The LRR rate in unirradiated patients with 1–3 positive nodes was 16.5% at 5 years, and was substantially higher than those seen today. Current systemic treatments usually include more effective strategies such as anthracycline and taxane chemotherapy, trastuzumab, and an aromatase inhibitor. Moreover, technological improvements and advances such as three-dimensional conformal radiotherapy in the delivery of PMRT have also made this approach more safe and effective. Following the spectrum theory, we can easily understand the complex interaction between respective contributions of systemic and locoregional treatments to the final outcomes, including survival and toxic effects [6]. Once & Kenji Sekiguchi kenjisek@luke.ac.jp

Randomized, prospective assessment of moisturizer efficacy for the treatment of radiation dermatitis following radiotherapy after breast-conserving surgery

Objective The effect of heparinoid moisturizer use after acute skin damage for patients receiving whole-breast radiotherapy after lumpectomy is understudied. Methods A total of 30 patients were randomly assigned to receive heparinoid moisturizer (Group M), and 32 patients comprised the control group (Group C). Patients in Group M were instructed to apply heparinoid moisturizer from 2 weeks following whole-breast radiotherapy, and to continue to use the moisturizer until 3 months after completion of whole-breast radiotherapy. Group C patients were instructed to not apply any topical moisturizer during the study period. The relative ratio of skin water content ratio (RWCR(t) = (It /Nt)/(I0/N0)) between irradiated and non-irradiated field was calculated. Signs and symptoms were also assessed. The primary endpoint was the difference in relative ratio of skin water content ratio between 2 and 4 weeks following whole-breast radiotherapy. Results In Group C, relative ratio of skin water content ratio dropped to 0.80 ± 0.15 at 2 weeks and maintained the low level at 4 weeks following whole-breast radiotherapy. Similarly, in Group M, relative ratio of skin water content ratio dropped to 0.81 ± 0.19 at 2 weeks (prior to application), however, it returned to baseline level (1.05 ± 0.23) at 4 weeks (2 weeks after application). The arithmetic difference of relative ratio of skin water content ratio in Group M was 0.24 ± 0.23 and was significantly larger than in Group C (0.06 ± 0.15; P < 0.01). Skin dryness and desquamation were less severe in Group M. Conclusions The application of heparinoid moisturizer for 2 weeks following whole-breast radiotherapy significantly increased water content and helped improve skin dryness and desquamation compared with no use of moisturizer.