Dose-volume analysis for quality assurance of interstitial brachytherapy for breast cancer.

PURPOSE/OBJECTIVE: The use of brachytherapy in the management of breast cancer has increased significantly over the past several years. Unfortunately, few techniques have been developed to compare dosimetric quality and target volume coverage concurrently. We present a new method of implant evaluation that incorporates computed tomography-based three-dimensional (3D) dose-volume analysis with traditional measures of brachytherapy quality. Analyses performed in this fashion will be needed to ultimately assist in determining the efficacy of breast implants. METHODS AND MATERIALS: Since March of 1993, brachytherapy has been used as the sole radiation modality after lumpectomy in selected protocol patients with early-stage breast cancer treated with breast-conserving therapy. Eight patients treated with high-dose-rate (HDR) brachytherapy who had surgical clips outlining the lumpectomy cavity and underwent computed tomography (CT) scanning after implant placement were selected for this study. For each patient, the postimplant CT dataset was transferred to a 3D treatment planning system. The lumpectomy cavity, target volume (lumpectomy cavity plus a 1-cm margin), and entire breast were outlined on each axial slice. Once all volumes were entered, the programmed HDR brachytherapy source positions and dwell times were imported into the 3D planning system. Using the tools provided by the 3D planning system, the implant dataset was then registered to the visible implant template in the CT dataset. The distribution of the implant dose was analyzed with respect to defined volumes via dose-volume histograms (DVH). Isodose surfaces, the dose homogeneity index, and dosimetric coverage of the defined volumes were calculated and contrasted. All patients received 32 Gy to the entire implanted volume in 8 fractions of 4 Gy over 4 days. RESULTS: Three-plane implants were used for 7 patients and a two-plane implant for 1 patient. The median number of needles per implant was 16.5 (range 11-18). Despite visual verification by the treating physician that surgical clips (with an appropriate margin) were within the boundaries of the implant needles, the median proportion of the lumpectomy cavity that received the prescribed dose was only 87% (range 73-98%). With respect to the target volume, a median of only 68% (range 56-81%) of this volume received 100% of the prescribed dose. On average, the minimum dose received by at least 90% of the target volume was 22 Gy (range 17.3-26.9), which corresponds to 69% of the prescribed dose. CONCLUSION: Preliminary results using our new technique to evaluate implant quality with CT-based 3D dose-volume analysis appear promising. Dosimetric quality and target volume coverage can be concurrently analyzed, allowing the possibility of evaluating implants prospectively. Considering that target volume coverage may be suboptimal even after radiographically verifying accurate implant placement, techniques similar to this need to be developed to ultimately determine the true efficacy of brachytherapy in the management of breast cancer.     

The 10-Year Local Recurrence and Partial Breast Radiotherapy for Early Breast Cancer Treated by Conservative Surgery

C onservative surgery for early breast cancer was proposed by Keynes in 1924 and has been one of the main therapeutic mea- sures. It has been confirmed by abundant literature that the efficacy of conservative surgery plus whole breast radiotherapy is the …     

T1-2N1M0早期乳腺癌术后放射治疗的研究进展

乳腺癌是危害女性健康的常见疾病,术后放疗(PMRT)可以提高患者生存率,减少乳腺癌转移及复发率,是治疗乳腺癌的重要方法.术后放疗对1～3个淋巴结阳性乳腺癌的治疗效果及预后影响仍是当前的讨论热点.本文就高危因素、分子分型、21基因检测、预后营养指数等对T1-2 N1 M0早期乳腺癌术后放疗的指导意义作一综述.     

T1-2N1M0期乳腺癌新辅助化疗后疗效分析及放疗选择的探讨

目的 评价T_1-2N₁M₀期乳腺癌新辅助化疗后辅助放疗对LC率的影响及地位。方法收集2005—2010年间收治的新辅助化疗患者资料,筛选出T_1-2N₁M₀人群,并对其辅助放疗的临床结果进行分析。共入组T_1-2N₁M₀患者144例,中位年龄45岁(23~72岁)。结果 术后30例(21%)获得乳腺原发灶和腋窝淋巴结pCR者均接受了辅助放疗,45例仅腋窝淋巴结阳性转阴性者中10例未接受辅助放疗,69例腋窝淋巴结转移仍为阳性者中6例未接受放疗,其余患者均接受了辅助放疗。全组中位随访时间88个月,46例复发转移(32%),其中pCR者5年LR率为3.0%。5年LR率新辅助化疗后腋窝淋巴结阳性转阴性者放疗组为7%、未放疗组为16%(P=0.181),腋窝淋巴结仍为阳性者放疗组为15.9%、未放疗组为33%(P=0.267)。全组pCR者DFS时间较非pCR者延长(P=0.017)。结论 新辅助化疗后获pCR者DFS期优于未获pCR者,获pCR患接受辅助放疗的LR率较低,腋窝淋巴结阳性转阴性者未能从术后辅助放疗中获益,而腋窝淋巴结转移仍为阳性者的LR率高,辅助放疗有获益趋势。     

T1N0M0乳腺癌临床病理特征和预后分析

目的：探讨T1N0M0乳腺癌患者的临床病理特征与预后关系。方法：收集2003-01-01-200912-31广东省妇幼保健院乳腺病防治中心住院治疗的137例T1N0M0乳腺癌患者的资料,回顾性分析临床病理特征与预后的关系。结果：共收治934例I～ⅢA期乳腺癌患者,其中T1N0M0乳腺癌137例,占14．7％。137例T1N0M0乳腺癌患者中有33例（24．1％）为T1mic,42例（30．7％）为T1a～T1b,62例（45．2％）为T1c。肿瘤大小与组织学分级（P=0．001）有关,与年龄（P=0．526）、ER／PR（P=0．371）、HER-2（P=0．624）、手术方式（P=0．479）和术后辅助化疗（P=0．066）无明显相关性。中位随访47个月,5例患者复发转移,其中1例患者死于肝转移,5年无病生存期（disease-freesurvival,DFS）为96．4％,5年总生存期（overallsurvival,OS）为99．3％。在单因素分析中,T1N0M0乳腺癌的5年DFS与肿瘤组织学分级（P=0．010）和ER／PR状态（P=0．043）有关,而与年龄（P=0．217）、肿瘤大小（P=0．880）、HER-2状态（P=0．769）、手术方式（P=0．477）和有无化疗（P=0．560）无关;在多因素分析中,仅肿瘤组织学分级是5年DFS的独立影响因素,P=0．045。组织学分级G1、G2和G3患者的5年DFS分别为100．0％、96．3％和84．2％,伴有组织学分级非G3患者的5年DFS（98．3％）优于伴有组织学分级G3（84．2％）的患者,P=0．005;G2（96．3％）和G1（100．0％）患者5年DFS差异无统计学意义,P=0．109。结论：肿瘤组织学分级是T1N0M0乳腺癌的5年DFS独立影响因素,肿瘤组织学分级高的患者预后差。肿瘤组织学分级可为T1N0M0乳腺癌的辅助化疗决策提供参考依据。     

Prognostic significance of pretreatment hemoglobin for local control and overall survival in T1-T2N0 larynx cancer treated with external beam radiotherapy

PURPOSE: To elucidate a relationship between pretreatment hemoglobin and local control in patients with T1-T2N0 larynx cancer treated with radiotherapy. METHODS AND MATERIALS: A total of 246 patients with T1-T2N0 cancer of the larynx were included in this analysis. Patients were treated using a median daily fraction of 200 cGy to a total median dose of 66 Gy within 47 days. Prognostic factors included pretreatment hemoglobin, age, gender, race, T stage, tumor subsite, beam energy, biologically equivalent dose, and therapy duration. RESULTS: Fifty patients developed local relapse, for an actuarial 5-year relapse-free rate of 77.3%. The actuarial 5-year survival rate was 69.8%. The pretreatment hemoglobin levels were assessed using the following hemoglobin quartiles: 10.1-13.3, 13.4-14.1, 14.2-14.9, and 15.0-18.3 g/dL. On Cox multivariate analysis, the pretreatment hemoglobin level predicted for local failure and poorer overall survival. The relative risk for 5-year local relapse by hemoglobin quartile was 2.70, 2.33, 1.91, and 1.00 (p = 0.034). The relative risk for poorer 5-year overall survival by hemoglobin quartile was 2.23 1.30, 0.80, and 1.00 (p <0.001). CONCLUSION: Pretreatment hemoglobin levels predicted for local control and overall survival for larynx cancer in a multivariate model. This relationship has potential therapeutic implications regarding correcting anemia before the initiation of radiotherapy for optimal outcome.     

Predicting aggressive outcome in T1N0M0 breast cancer

Despite the excellent overall prognosis, unpredictable breast cancer recurrences and deaths also occur among T1N0M0 patients. We have evaluated clinically applicable methods for identifying aggressive outcome in T1N0M0 breast cancer. The material is based on aggressive T1N0M0 invasive ductal and lobular carcinomas diagnosed in Turku University Hospital and Jyv?skyl? Central Hospital, Finland, during 1987-1997. We studied all the T1N0M0 breast cancers that had led to recurrency or death (n=21, 95% T1cN0M0) during the follow-up period (4-14 years). The study is based on statistical analyses of matched case-control data in which the prognostic factors of each individual patient with aggressive disease were compared with control patients (n=45) individually matched by tumour size, age at diagnosis, histological type of tumour and length of follow-up. The cancer cases were examined for clinically applicable conventional and immunohistochemical pathologic prognostic factors. High Ki-67 immunopositivity was the strongest prognosticator of breast cancer death or recurrence in T1N0M0 breast cancer. Also, high p53 immunopositivity, low oestrogen receptor immunopositivity and Her-2/neu oncogene amplification by chromogen in situ hybridisation were reliable indicators of unfavourable outcome. Our statistical methods also allowed us to determine for the present material a range of clinical significance for each immunohistochemical prognostic feature with the associated relative risk for breast cancer death and recurrence. The paper suggests guidelines for predicting aggressive outcome in T1N0M0 breast cancer.     

Patterns of breast relapse after local excision +/- radiotherapy for early stage breast cancer

One hundred patients with breast recurrence have been identified from patients at the Royal Marsden Hospital, treated by local excision +/- radiotherapy for early stage primary invasive breast cancer between 1961 and 1985. The mean follow-up was 58 months (range 1 month - 19 years). In 74/100 patients, breast recurrence occurred within the breast parenchyma, was not associated with systemic relapse and carried a relatively good prognosis with a median survival of 77 months from the time of breast relapse. In 67 patients with parenchymal relapse in whom the site of relapse could be reliably compared with that of the original tumour, 60 (90%) patients developed recurrent tumours at or close to the primary site. In 24/100 patients, breast recurrence occurred in the overlying skin and in only two of these patients (2% of total) did recurrence actually occur within the scar tissue. Skin relapse was associated with systemic relapse and carried a relatively poor prognosis with a median survival of 36 months from the time of recurrence. The pattern of breast relapse was similar in irradiated and unirradiated patients. Skin relapse appears to be a manifestation of metastatic disease while parenchymal relapse may represent regrowth of primary tumour. This pattern of breast relapse questions the requirement for radiotherapy to the whole breast after local excision for early stage breast cancer.     

高剂量率腔内放疗治疗宫颈癌临床分析

目的 评价高剂量率腔内放疗治疗宫颈癌的疗效及并发症。方法 242例宫颈癌患者,其中Ⅰ期2例,Ⅱ期135例,Ⅲ期102例,Ⅳ期3例;鳞癌225例,腺癌16例,腺鳞癌1例,采用8MVX线或60Co γ线体外放疗及137Cs腔内放疗。结果 Ⅱ期、Ⅲ期患者5年生存率分别为75.60%和50.9％。放射性直肠炎及放射性膀胱炎发生率分别为11.2%和7.9％。结论 高剂量率腔内放疗是治疗宫颈癌的一种可行、有效的方法,疗效较好,并发症轻微,但对高危宫颈癌患者,需强调综合治疗。     

Are prognostic factors for local control of breast cancer treated by primary radiotherapy significant for patients treated by mastectomy?

Recent follow-up studies of patients with mammary carcinoma treated with breast-conserving primary radiotherapy identified a triad of pathologic features significantly associated with local treatment failure. These unfavorable characteristics of the primary tumor were: poor or undifferentiated nuclear grade; intraductal carcinoma within the tumor mass; and intraductal carcinoma in breast tissue outside the perimeter of the primary lesion. The current study was undertaken to assess the impact of these same factors on the prognosis of 573 consecutively treated women, with invasive duct carcinomas 5 cm or less in diameter, and who underwent mastectomy. Histologic sections of all primary tumors were reviewed, and the lesions were classified according to the distribution of intraductal carcinoma present: only within the tumor (IN, 247 cases, 43%), only outside the tumor (OUT, 25 cases, 4%), within the outside (IN-OUT, 158 cases, 28%), or not seen (IFDC, 143 cases, 25%). The median follow-up period for the entire series was 56 months. Ninety-five (17%) patients were dead of disease (median time to death, 36 months). Variables that proved to be statistically significant for overall survival were nodal status (P less than 0.001), nuclear grade (P less than 0.03), and histologic grade (P less than 0.007). Nodal status (P less than 0.001), histologic grade (P less than 0.001), and tumor size (P = 0.01) were significant predictors of disease-free survival. The pattern of intraductal carcinoma, when present, was not predictive of the risk for recurrence or survival in women treated by mastectomy. These findings provide a rationale for additional surgical treatment for women whose tumors have features more likely to be associated with local failure following primary radiotherapy. To permit more detailed pathologic examination of the primary lesion, the initial excision should be carried out separately from the treatment when limited resection and radiation are to be considered as a treatment option.     

Dose-volume histogram analysis as predictor of radiation pneumonitis in primary lung cancer patients treated with radiotherapy

PURPOSE: To determine the relationship between various parameters derived from lung dose-volume histogram analysis and the risk of symptomatic radiation pneumonitis (RP) in patients undergoing radical radiotherapy for primary lung cancer. METHODS AND MATERIALS: The records of 156 patients with lung cancer who had been treated with radical radiotherapy (>/=45 Gy) and for whom dose-volume histogram data were available were reviewed. The incidence of symptomatic RP was correlated with a variety of parameters derived from the dose-volume histogram data, including the volume of lung receiving 10 Gy (V(10)) through 50 Gy (V(50)) and the mean lung dose (MLD). RESULTS: The rate of RP at 6 months was 15% (95% confidence interval 9-22%). On univariate analysis, only V(30) (p = 0.036) and MLD (p = 0.043) were statistically significantly related to RP. V(30) correlated highly positively with MLD (r = 0.96, p < 0.001). CONCLUSION: V(30) and MLD can be used to predict the risk of RP in lung cancer patients undergoing radical radiotherapy.     

T1-2N0-1M0期乳腺癌保乳术后大分割调强放疗近期临床观察

目的:观察T1-2N0-1M0期乳腺癌保乳术后大分割调强放疗的疗效、美容效果及不良反应。方法:选择2011年11月-2012年11月间就诊于山西省肿瘤医院乳腺疾病诊治中心的乳腺癌保乳患者41例,予大分割调强放疗,全乳计划靶体积43.5Gy/15次,瘤床区电子线补量8.7Gy/3次,2.9Gy/次,5次/周,疗程共24天。局部区域控制率和总生存率用Kaplan-Meier法计算。结果:中位随访时间27个月,随访率100%。3年局部区域控制率、生存率均为100%,急性放射性皮肤反应Ⅰ级4例,Ⅱ级3例;血液系统不良反应白细胞下降Ⅰ级5例,Ⅱ级3例,Ⅲ级2例;急性放射性肺炎I级2例,晚期放射性肺炎1例;患肢水肿轻度2例。放疗前、后美容效果评价优秀+良好率为95.1%、87.8%,放疗后1、3、6、12个月优秀+良好率均为90.2%。结论:早期乳腺癌保乳术后调强大分割放疗疗效和美容效果较好,且不良反应发生率低,可以缩短放疗时间。     

鼻咽癌T3N0-1M0期单纯放疗和同期放化疗疗效回顾分析

 目的　回顾分析T3N0~1M0期鼻咽癌患者临床资料,探讨单纯放射治疗与同期放化疗两种治疗方式与预后的关系。方法　中山大学肿瘤防治中心2004年1月至12月收治的经病理学证实的初治鼻咽癌患者781例,均有完整鼻咽和颈部MRI资料,且均无远处转移。按照2008中国鼻咽癌分期标准重新分期,82例行单纯放疗或同期放化疗的T3N0~1M0期患者入组,分为单纯放疗（A组）46例,同时期放化疗（B组）36例。结果　两组患者的临床资料具有可比性,单因素分析显示A组和B组的5年总生存（OS）率分别为93.5 %和100 %（P＝0.046）,5年无瘤生存（DFS）率分别为85.2 %和91.7 %（P＝0.498）。N分期是鼻咽癌DFS的影响因素（P＝0.026）。分层分析显示：T3N0M0期患者A组和B组5年OS率分别为94.7 %和100 %（P＝0.432）;T3N1M0期A组和B组5年OS率分别为92.6 %和100 %（P＝0.066）;T3N1M0期A组和B组5年DFS率分别为73.7 %和89.3 %（P＝0.244）。多因素分析显示,同期放化疗不是 T3N0~1M0期鼻咽癌患者OS的独立预后因素（HR＝0.019;95 % CI 0～21.793）,N分期不是影响T3N0~1M0期鼻咽癌患者DFS的独立预后因素（HR＝0.203;95 % CI 0.135～1.231×104）。结论　T3N0M0期患者同期放化疗与单纯放疗疗效无差异, T3N1M0期患者行同期放化疗能否改善生存有待进一步研究。     

Conservative surgery for T2 > 3 cm, T3 N0 N1 M0 breast cancer after induction chemotherapy

Induction chemotherapy (IC) provides in more than 20% of cases a complete shrinkage of the tumor. This down staging is a new challenge for the surgeons for breast conservative procedure. Although, IC has become the standard of care for breast cancer T2 > 3 cm T3 N0 N1 M0. No guidelines have devoted attention to the surgical problems due to this down staging after IC. Location and size of the tumor before IC have to be studied and outlined by the surgeon himself. During surgery, the residual tumor volume and how much mammary gland must be removed are very difficult to determine. The maximum volume of mammary gland to be removed after IC around the primary site of the tumor before IC is the volume which permits a good cosmetic reconstruction of the breast. After IC, in spite of an important downstaging, an axillary clearance must be done. For N0 patients, sentinel lymph node biopsy could be performed before IC. If the sentinel node is p N0, axillary clearance could be avoided.     

Dosimetric comparison of normal structures associated with accelerated partial breast irradiation and whole breast irradiation delivered by intensity modulated radiotherapy for early breast cancer after breast conserving surgery

Purpose

To assess the heart and lung dosimetry results associated with accelerated partial breast irradiation intensity-modulated radiotherapy (APBI-IMRT) and whole breast field-in-field intensity-modulated radiotherapy (WBI-FIF-IMRT).

Methods

A total of 29 patients with early-stage breast cancer after lumpectomy were included in this study. APBI-IMRT and WBI-FIF-IMRT plans were generated for each patient. The dosimetric parameters of ipsilateral lung and heart in both plans were then compared with and without radiobiological correction.

Results

With and without radiobiological correction, the volume of ipsilateral lung showed a substantially lower radiation exposure in APBI-IMRT with moderate to high doses (P < 0.05) but non-significant increases in volume of ipsilateral lung in 2.5 Gy than WBI-FIF-IMRT (P > 0.905).There was no significant difference in volume of ipsilateral lung receiving 1, 2.5, and 5 Gy between APBI-IMRT and WBI (P > 0.05) in patients with medial tumor location, although APBI-IMRT exposed more lung to 2.5 and 5 Gy. APBI-IMRT significantly decreases the volume of heart receiving low to high doses in left-sided breast cancer (P < 0.05).

Conclusion

APBI-IMRT can significantly spare the volume of heart and ipsilateral lung receiving moderate and high dose. Non-significant increases in volume of the ipsilateral lung exposed to low doses of radiation were observed for APBI-IMRT in comparison to WBI-FIF-IMRT, particularly in patients with medial tumor location. With the increasing interest in APBI-IMRT, our data may help clinicians individualize patient treatment decisions.     

Acute toxicity of intraoperative radiotherapy and external beam-accelerated partial breast irradiation in elderly breast cancer patients

Background and purpose

We investigated the acute toxicity of accelerated partial breast irradiation using external beam (EB-APBI) or intraoperative radiotherapy (IORT) techniques in elderly breast cancer patients.

Materials and methods

Women ≥ 60 years with unifocal breast tumors of ≤ 30 mm were eligible for this prospective multi-center cohort study. IORT was applied with electrons following lumpectomy (23.3 Gy). EB-APBI was delivered using 3D-CRT or IMRT in 10 daily fractions of 3.85 Gy within 6 weeks after surgery. Acute toxicity was scored using the CTCAE v3.0 at 3 months after treatment. Patient-reported symptoms were analyzed using visual analogue scales (VAS) for pain and fatigue (scale 0–10), and single items from the EORTC QLQ-C30 and Breast Cancer questionnaires.

Results

In total, 267 (IORT) and 206 (EB-APBI) patients were available for toxicity analysis. More patients experienced ≥ grade 2 CTCAE acute toxicity in the IORT group (10.4% IORT and 4.9% EB-APBI; p = 0.03); grade 3 toxicity was low (3.3% IORT and 1.5% EB-APBI; ns); and no grade 4 toxicity occurred. EB-APBI patients experienced less fatigue direct postoperatively (EORTC p < 0.00, VAS p < 0.00). After 3 months only pain, according to the VAS scale, was significantly worse in the EB-APBI group (p < 0.00).

Conclusion

Acute toxicity after IORT and EB-APBI treatment is acceptable.

     

Analysis of the Prognosis for Patients with Stage T3N0-1M0 Nasopharyngeal Carcinoma Treated by Chemotherapy Combined with Radiotherapy

OBJECTIVE To investigate the relationship between the therapeutic modality and prognostic factors for the patients with T3N0-1M0 nasopharyngeal carcinoma. METHODS The clinical data from 127 cases of T3N0-1M0 nasopharyngeal carcinoma patients with initial treatment, during the period from January 4th, 2000 to November 12th, 2001, were retrospectively analyzed. The cases were divided into Group A with simple radiotherapy (90) and Group B with the radiation therapy combined with chemotherapy (37), based on various patients' conditions. In group B, inductive chemotherapy was conducted for 18 cases, inductive chemotherapy plus homochronous chemotherapy for 5 and homochronous chemotherapy for 14. RESULTS The 5-year overall survival (OS) in the groups A and B was 73.4% and 72.3% respectively (P>0.05); the cancer-correlated survival (CCS) in the 2 groups was 76.4% and 72.3% respectively (P>0.05); the disease-free survival (DFS) in group A and B was 65.5% and 71.7% respectively (P<0.05). A multiple analysis showed that the mode of radiation therapy plus chemotherapy was a favorable independent impact factor for DFS. CONCLUSION Chemotherapy plus radiotherapy can improve the DFS of patients with T3N0-1M0 nasopharyngeal carcinoma, but fails to prolong the survival time of the patients. The modality of chemotherapy plus radiotherapy is not the necessary choice in treatment of patients with T3N0-1M0 nasopharyngeal carcinoma.     

Partial breast irradiation versus whole breast radiotherapy for early-stage breast cancer: a decision analysis

PURPOSE: To compare the quality-adjusted life expectancy between women treated with partial breast irradiation (PBI) vs. whole breast radiotherapy (WBRT) for estrogen receptor-positive early-stage breast cancer. METHODS AND MATERIALS: We developed a Markov model to describe health states in the 15 years after radiotherapy for estrogen receptor-positive early-stage breast cancer. Breast cancer recurrences were separated into local recurrences and elsewhere failures. Ipsilateral breast tumor recurrence (IBTR) risk was extracted from the Oxford overview, and rates and utilities were adapted from the literature. We studied two cohorts of women (aged 40 and 55 years), both of whom received adjuvant tamoxifen. RESULTS: Assuming a no evidence of disease (NED)-PBI utility of 0.93, quality-adjusted life expectancy after PBI (and WBRT) was 12.61 (12.57) and 12.10 (12.06) years for 40-year-old and 55-year-old women, respectively. The NED-PBI utility thresholds for preferring PBI over WBRT were 0.923 and 0.921 for 40-year-old and 55-year-old women, respectively, both slightly greater than the NED-WBRT utility. Outcomes were sensitive to the utility of NED-PBI, the PBI hazard ratio for local recurrence, the baseline IBTR risk, and the percentage of IBTRs that were local. Overall the degree of superiority of PBI over WBRT was greater for 55-year-old women than for 40-year-old women. CONCLUSIONS: For most utility values of the NED-PBI health state, PBI was the preferred treatment modality. This result was highly sensitive to patient preferences and was also dependent on patient age, PBI efficacy, IBTR risk, and the fraction of IBTRs that were local.