Local-regional Radiotherapy Research Articles

Combining Radiotherapy with Chemotherapy and Immunotherapy as First-Line Treatment for De Novo Metastatic Nasopharyngeal Carcinoma: A Dual-Center Retrospective Analysis

Local regional radiotherapy combined with systemic chemotherapy significantly improves the prognosis of patients with metastatic nasopharyngeal carcinoma (NPC). Immunochemotherapy has become the first-line treatment for initial metastatic NPC. This study evaluated the safety and efficacy of local regional radiotherapy combined with immunochemotherapy as the first-line treatment of metastatic NPC. Patients with histologically proven de novo metastatic NPC who received immunotherapy and chemotherapy followed by local-regional radiotherapy were included from 2 cancer centers. Toxicity and treatment response were assessed using CTCAE 5.0 and RECIST 1.1, respectively. Overall survival (OS) and progression free survival (PFS) were analyzed using the Kaplan-Meier method. From 2019 to 2021, a total of 16 patients were retrospectively analyzed. The median age was 44.5-year-old (range 16-76). Patients with ≥3 metastatic lesions accounts for 58.8%. Bone metastasis was the most common metastatic site. The chemotherapy regimens were paclitaxel/gemcitabine and cisplatin. Toripalimab, camrelizumab and sintilimab were used for immunotherapy. All patients completed the local regional radiotherapy with 69.96Gy for primary nasopharyngeal tumor and positive lymph nodes, 60.06Gy for high-risk region and 50ཞ54.45Gy for low-risk region. Seven patients underwent radiotherapy for metastatic lesions. The median follow-up was 20.5 months (range 6-38 months). Two-year OS was 100%. Three patients experienced distant progression. One-year and 2-year PFS rate was 93.8% and 76.7%, respectively. After combination of chemotherapy and immunotherapy, the overall response rate (ORR) was 93.7% with a complete response (CR) of 6.3%. At the end of radiotherapy, the ORR was 100%. Nine patients (56.3%) achieved CR. Radiotherapy related acute severe (grade 3 or higher) toxicity was dermatitis (1/16, 6.3%) and mucositis (2/16, 12.5%). Immunotherapy related hypophysitis and capillary hyperplasia was 6.3% and 6.3%, respectively. No long-term toxicity was observed. Loco-regional radiotherapy provided a promising efficacy with modest toxicity for patients with metastatic nasopharyngeal carcinoma who received immunochemotherapy.

EP-276 Tall Cell Carcinoma with Reverse Polarity (TCCRP) of the breast; a rare form of breast cancer

Abstract Aim A case report on the diagnosis and treatment of this rare low grade triple negative breast cancer. Case Report A 41 year old female presented with a palpable left breast lump. Family history includes a sister with a rare myeloproliferative disorder. On examination, a left breast lower outer quadrant 2–3 cm hard irregular lump was palpable. Mammography and ultrasound revealed a 25 mm suspicious lesion (which was biopsied), with normal appearing lymph nodes. Results Biopsy revealed a grade 2 invasive apocrine carcinoma. Oestrogen and Herceptin receptors negative. Breast conserving surgery with sentinel lymph node biopsy was performed. Histology revealed a 22 mm well circumscribed tumour with nests of epithelial cells in micropapillary pattern with apocrine like appearance. The most striking feature was that the nuclei were at the apical rather than the basal poles of the epithelial cells (reverse polarity). No lymphovascular invasion present. Lymph nodes were negative (0/3). Diagnosis was then confirmed by molecular testing. Conclusion Tall cell carcinoma with reverse polarity (TCCRP)1, a rare cancer resembling tall cell variant of papillary thyroid carcinoma, was first reported by Eusebi et al in 20032. Although morphologically similar to metastatic papillary thyroid cancer, neither the immunohistochemical markers nor genetic profiles have established any connection3. Accurate diagnosis of TCCRP is important as it carries an excellent prognosis. Treatment is local regional radiotherapy. There is no indication for systemic therapy in this case, due to its indolent low metastatic potential.

Changes in radiotherapy fractionation-breast cancer.

Conventional fractionation for half a century has been justified on the basis that 2.0 Gy fractions spare dose-limiting late-responding normal tissues to a greater degree than cancerous tissues. Early indications that breast cancer responds more strongly to fraction size than many other common cancers were followed several decades of investigation, but there is now reliable Level I evidence that this is the case. Four randomised trials testing fraction sizes in the range 2.7–3.3 Gy have reported 10-year follow up in almost 8000 patients, and they provide robust estimates of α/β in the range of 3 Gy. The implication is that there are no advantages in terms of safety or effectiveness of persisting with 2.0 Gy fractions in patients with breast cancer. 15- or 16-fraction schedules are replacing the conventional 25-fraction regimen as a standard of care for adjuvant therapy in an increasing number of countries. A number of concerns relating to the appropriateness of hypofractionation in patient subgroups, including those treated post-mastectomy, advanced local-regional disease and/or to lymphatic pathways are addressed. Meanwhile, hypofractionation can be exploited to modulate dose intensity across the breast according to relapse risk by varying fraction size across the treatment volume. The lower limits of hypofractionation are currently being explored, one approach testing a 5-fraction schedule of local-regional radiotherapy delivered in 1 week.

Should radiotherapy after primary systemic therapy be administered with the same recommendations made for operable breast cancer patients who receive surgery as first treatment? A critical review.

Primary systemic therapy is not only used in patients with locally advanced inoperable non-metastatic breast cancer but also for operable stage II and III cancer aimed at breast conservation. The indications for local-regional radiotherapy for patients who receive primary systemic therapy are still evolving. The purpose of this article is to provide a comprehensive discussion of how primary systemic therapy in operable breast cancer patients could affect the indications of radiotherapy to optimize local-regional treatment. An overview of available literature data regarding neoadjuvant treatment and radiotherapy is analyzed and discussed. Considering the variability of data on this issue, an appropriate approach could still be to tailor treatment decision to the individual clinical case.

Abstract ES4-3: What is the value of internal mammary chain RT and how can we deliver it safely?

Abstract The 2014 systematic overview of post-mastectomy radiotherapy (RT) in pN+ patients randomized ± local-regional RT reported absolute 7.9% (SE 3.1) and 9.3% (SE 2.7) reductions in 20-year breast cancer mortality in women with 1-3 and 4+ positive nodes, respectively [1]. Most patients were given RT to axilla, supraclavicular fossa (SC) and internal mammary chain (IM); hence, it is impossible to calculate what IM-RT contributes. Three randomised trials (French n=1334; MA.20 n=1832; EORTC n=4004) have specifically tested IM-RT, 2 of which included medial SC in the randomisation. All patients received axillary dissection (AD) and mastectomy/tumour excision, with an average 62% axillary node positivity. Table 1 lists the treatments delivered. Table 1TreatmentFrenchMA.20EORTCSurgeryMastectomy + ADMastectomy/Breast conservation + ADMastectomy/Breast conservation + ADRT ControlChest wall + axillary apex + medial SCChest wall or breastChest wall or breastRT Test (in addition to Control)IMIM + medial SCIM + edial SC No trial detected a statistically significant benefit in overall survival (OS), but early metanalysis of the 3 studies suggests a statistically significant improvement in OS (HR 0.88 95% CI 0.80-0.97) in patients allocated IM-RT with/without additional SC-RT [2]. Disease-free (DFS), metastasis-free (MFS) and overall survival (OS) benefits are shown in Table 2. Table 2ResultsFrenchMA.20EORTCDFSAbsolute 3.3% gain (10yr, NS)HR 0.67 (95% CI 0.52-0.87)HR 0.89 (95% CI 0.80-1.00)MFS-HR 0.64 (95% CI 0.47-0.85)HR 0.86 (95% CI 0.76-0.98)OSAbsolute 3.3% gain (10yr, NS)HR 0.76 (95% CI 0.56-1.05) Absolute 1.6% gain (5yr, NS)HR 0.87 (95% CI 0.76-1.0) Absolute 1.6% gain (10yr, NS) The sole trial (French) to report arm swelling recorded a small (3.1%) absolute excess of grade 2 arm lymphedema after IM-RT; the other 2 trials reported no excess cardiac toxicity. Only the French trial is published as a full manuscript, and until this is the case for the other 2 trials, it is impossible to say how specific and robust guidelines will be. Assuming the benefits of IM-RT rely on eradication of IM metastases, factors associated with risk of IM involvement include macroscopic involvement of multiple axillary nodes and central/medial quadrant tumours. Recommendations based on sentinel IM node biopsy, lymphoscintigraphy or positron emission tomography are likely to be may be desirable. Accurate mediastinal staging may not resolve all issues, as the current debate challenging the need to treat the axilla in women with axillary micrometastases illustrates. The 2 commonly-used techniques involve simple 3D forward planned dosimetry that is usually able to satisfy standard constraints for organs at risk. The IM is encompassed within wide tangential beams in 1 technique, and as an extension of an anterior SC beam in the other. Example of each will be presented. 1. EBCTCG. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: Meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet, 2014. 383: p. 2127-25. 2. Budach, W., et al., Adjuvant radiotherapy of regional lymph nodes in breast cancer - a meta-analysis of randomized trials. Radiat Oncol, 2013. 8: p. 267. Citation Format: John R Yarnold. What is the value of internal mammary chain RT and how can we deliver it safely? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES4-3.

Reducing Local Therapy in Patients Responding to Preoperative Systemic Therapy: Are We Outsmarting Ourselves?

There is growing interest in the use of preoperative (neoadjuvant) chemotherapy for patients with localized breast cancer. Originally, it was hypothesized that such early use of chemotherapy might improve survival, compared with standard postsurgical adjuvant systemic therapy, but this has not proven to be the case. Nonetheless, the primary tumor response is likely a barometer for tumor sensitivity to therapy and may be used to help guide decisions regarding additional systemic therapy. Furthermore, preoperative chemotherapy can increase the fraction of women eligible for breast-conservation therapy. A seemingly logical extension of this latter observation is the hypothesis that one can further reduce local therapies in patients responding well to initial chemotherapy. For example, studies are under way to omit (or limit) radiotherapy (RT) in patients who present with positive axillary nodes and experience pathologic complete response in the nodes to preoperative chemotherapy (eg, NSABP [National Surgical Adjuvant Breast and Bowel Project] B-51/RTOG [Radiation Therapy Oncology Group] 1304). In the NSABP/RTOG study, patients with involved axillary nodes (histologically confirmed) are treated with neoadjuvant chemotherapy. Those who are node negative at subsequent mastectomy are randomly assigned to postmastectomy RT (PMRT) to the chest wall and regional nodes. Similarly, patients who undergo subsequent breast conservation surgery and whose nodes have become negative after preoperative chemotherapy will be randomly assigned to breast RT regional nodal RT. We appreciate the importance of the question being asked in these studies and support their conduct. Defining patient subgroups that do (or do not) benefit from our therapies is an important goal. It is possible that response to preoperative chemotherapy predicts for the potential benefit of local regional RT (and hence theassociatedtherapeutic ratio).Responders topreoperativechemotherapy may have a lesser need for additional local regional RT. However, we believe the converse may be true: that the potential survival benefits of local therapies are likely highest among responders to preoperative chemotherapy. Consider the more typical clinical scenario for node-positive patients who undergo initial mastectomy, followed by adjuvant chemotherapy (Fig 1). In that setting, the addition of PMRT improves overall survival (OS) by approximately 6% to 9%. This group includes both responders and nonresponders to chemotherapy, althoughidentificationofthesesubgroupsisnotpossible,becausechemotherapy is administered postoperatively. If it is true that responders to neoadjuvant chemotherapy derive lesser survival gains with PMRT, it must follow that nonresponders derive greater gains, because the OS benefit should still be 6% to 9% (ie, sequencing of surgery and chemotherapy should not alter this; Fig 1, lower panel). An analogous situation exists for patients undergoing breast conservation. The NCIC Clinical Trials Group MA.20 study reported improvements in locoregional control and distant disease-free survival and a trend in OS with the addition of nodal RT to breast RT in patients undergoing lumpectomy followed by chemotherapy. If responders to preoperative chemotherapy derive lesser gains with nodal RT, nonresponders should derive greater gains (again, to make the math work). As we discuss here, the evidence suggests that the opposite may be true: namely, that responders to systemic therapy might derive the most survival benefit from RT. Mastectomy Chemotherapy 6%-9%

Carcinoma of the Ectopic Breast

A 43-year-old woman presented with bilateral ectopic breasts in both the axillae in Chittagong Medical College Hospital in July 1996. She was diagnosed having carcinoma in the left ectopic breast. She was successfully treated with local surgical excision and regional lymph node dissection, adjuvant chemotherapy, loco-regional radiotherapy and hormone therapy. The patient continued tamoxifen for 5 years. Till last follow-up in December 2011, the patient was asymptomatic without any evidence of residual disease or local recurrence and evidence of metastases. DOI: http://dx.doi.org/10.3329/jemc.v3i1.13874 J Enam Med Col 2013; 3(1): 47-49

The Relationship between Patterns of Recurrence and Radiotherapy Field Design in Women with Locally Advanced Breast Cancer

Local regional radiotherapy (RT) is a key component in the multi-modal management of women with locally advanced breast cancer (LABC). An analysis was undertaken to determine the frequency and patterns of recurrence in relation to the field borders used in RT treatment in women with LABC.

Abnormalities by pulmonary regions studied with computer tomography and clinical correlation following local-regional radiotherapy for breast cancer

Background:Adjuvant local-regional radiotherapy (RT) is commonly recommended for breast cancer patients. Postoperative adjuvant RT for breast cancer is associated with pulmonary side effects. This study was undertaken to measure the RT-induced pulmonary radiological changes with computer tomography (CT) scan using a CT-adapted modification of the Arriagada classification system, and to correlate these changes to RT techniques, pulmonary complications, and pulmonary function. The aim of the study is to study pulmonary radiological abnormalities with CT following different RT techniques for breast cancer, and their correlation to pulmonary complications and reduction in forced vital capacity (FVC).Materials and Methods:CT scans of the lungs were performed prior to and 4 months following RT in 53 breast cancer patients treated with local-regional RT. The radiological abnormalities were analyzed with a CT-adapted modification of a classification system originally proposed by Arriagada. The patients were monitored for RT-induced pulmonary complications. FVC was measured prior to and 6 months following RT. Statistical analysis used were that increasing CT scores were correlated with pulmonary complications (P < 0.001). The correlation between density grade (0-3, 4-9) and pulmonary complications (no complication vs slight/severe) was tested using Chi-square exact test for trend (2-sided). In addition, correlation between CT scores and FVC was done.Results:Increasing CT scores were correlated with pulmonary complications (P < 0.001). The mean reduction of FVC for patients scoring 4-9 (-220 ml) was larger than for patients scoring 0-3 (-15 ml) (Spearson correlation coefficient significant at 0.01 level 2 tailed). But the mean reduction of FVC with greater volume of lung irradiated was not statistically different than lesser volume of lung irradiated (P > 0.05).Conclusions:Radiological abnormalities detected on CT images and scored with a modification of Arriagada's classification system can be used as an objective endpoint for pulmonary side effects in postmastectomy RT.

Should Radiotherapy after Primary Systemic Therapy be Administered with the Same Recommendations Made for Operable Breast Cancer Patients who Receive Surgery as first Treatment? A Critical Review

Primary systemic therapy is not only used in patients with locally advanced inoperable non-metastatic breast cancer but also for operable stage II and III cancer aimed at breast conservation. The indications for local-regional radiotherapy for patients who receive primary systemic therapy are still evolving. The purpose of this article is to provide a comprehensive discussion of how primary systemic therapy in operable breast cancer patients could affect the indications of radiotherapy to optimize local-regional treatment. An overview of available literature data regarding neoadjuvant treatment and radiotherapy is analyzed and discussed. Considering the variability of data on this issue, an appropriate approach could still be to tailor treatment decision to the individual clinical case.

Local-regional radiotherapy and surgery is associated with a significant survival advantage in metastatic breast cancer patients

There is growing evidence of a survival benefit for metastatic breast cancer patients receiving surgery of the primary tumor. We investigated whether or not adjuvant radiotherapy can improve survival. Women diagnosed between 1988 and 2003 with metastatic, histologically confirmed unilateral primary breast cancer were selected from the SEER Program. Overall survival and specific survival were computed by the Kaplan-Meier method. Treatment hazard ratios of breast-conserving surgery or mastectomy versus no surgery, and radiotherapy versus none, were computed by Cox regression adjusting for period of diagnosis, age, marital status, race, histology, grade, and hormone receptors. Of 8761 women, radiotherapy was given to 1473 of 3905 who did not undergo surgery, to 882 of 2070 who underwent breast-conserving surgery, and to 1103 of 2786 mastectomy patients. Median overall survival was: for no surgery, 14 months; for breast-conserving surgery, 23 months; and for mastectomy, 28 months (P < 0.0001). The median overall survival of radiotherapy versus none was respectively 16 vs. 13 months without surgery (P = 0.0003), 28 vs. 20 months for breast-conserving surgery patients (P < 0.0001), and 28 vs. 28 months among mastectomy patients (P = 0.895). Multivariate analysis showed relative mortality reductions of 28% by breast-conserving surgery, 42% by mastectomy, and 10% by radiotherapy. Specific survival showed comparable results. Surgery and radiotherapy were associated with a significant survival advantage. We argue that local therapy should be considered even in metastatic disease.

Reduction of radiation pneumonitis by V20-constraints in breast cancer

IntroductionAdjuvant local-regional radiotherapy (LRRT) is routinely recommended for breast cancer patients. It is well known being related to pulmonary side-effects. We studied post-RT radiological changes on X-ray and CT, and correlated the findings with Quality of Life (QoL), common dosimetric factors and co-variates. The results were compared with a previously reported cohort of 137 irradiated women.Methods88 women underwent chest X-ray and CT pre-and 4-5 months after 3-D planned LRRT, minimizing the dose to the ipsilateral lung to V20 < 30%. The lung field was divided into 3 regions and the development of post-RT density changes were graded (0-3). Patients with radiological changes were compared with non-responders. Clinical symptoms were registered and data on patient and treatment related co-variates were gathered prospectively. The ipsilateral lung dosimetric factors V13, V20, V30 and mean dose were calculated and QoL was assessed before and 4 months after RT.ResultsThe use of dose-volume constraints significally reduced moderate-severe radiological changes on chest X-ray compared with our earlier study (Chi square trend test: p < 0.001). Symptomatic pneumonitis was also rare in the present study. No agreement was found between CT and chest X-ray as diagnostic tools for post-RT pneumonitis. V13 correlated independently with radiological changes on CT (logistic regression: p = 0.04; ROC area: 0.7). The Co-variates smoking habits, age, chemotherapy, endocrine or trastuzumab therapy did not influence the outcome on multivariate analysis. QoL changes in physical function, i.e. fatigue, dyspnoea were not detected but there was a trend for a worse recovery after chemotherapy in patients with high V13 (Spearman Rank Correlation: p < 0.05).ConclusionsThe use of dose-volume constraints significantly reduced post-RT radiological changes on chest X-ray in LRRT for BC. The lung changes on CT were also generally limited when we used this strategy and was not always picked up on chest X-ray. Variation in V13 alone was correlated with occurrence of lung changes on CT.

Impact of High-Dose Chemotherapy on the Ability to Deliver Subsequent Local–Regional Radiotherapy for Breast Cancer: Analysis of Cancer and Leukemia Group B Protocol 9082

Impact of High-Dose Chemotherapy on the Ability to Deliver Subsequent Local–Regional Radiotherapy for Breast Cancer: Analysis of Cancer and Leukemia Group B Protocol 9082

Importance of Dosimetric Factors and Co-variates on Pulmonary Radiological Changes after Local-regional Radiotherapy (LRRT) for Breast Cancer (BC)

Purpose/Objective(s)It is well known that LRRT for BC is associated with pulmonary radiological changes. We studied post-RT lung changes on X-ray and CT and correlated the findings with common dosimetric factors and co-variates, and compared the outcome with a previously reported cohort of 137 irradiated women.Materials/Methods88 women underwent chest X-ray and CT pre- and 4 months after 3-D planned LRRT aimed at maximizing the dose to the ipsilateral lung to V20 < 30%. The lung field was divided in 3 sections and density changes were graded (0-3). Patients with radiological changes were compared with non-responders. Data on clinically important patient- and treatment-related co-variates were gathered prospectively and correlated with post-RT lung changes, as was dosimetric factors (V13, V20, V30 and mean dose).ResultsThe use of dose-volume constraints significantly reduced moderate-severe radiological changes on X-ray compared with the earlier treatment series (Chi square trend test: p < 0.001). Symptomatic pneumonitis was also very rare in the present study. There was no agreement on CT and X-ray as diagnostic tools for post-RT pneumonitis. V13 was most strongly and independently correlated with radiological changes on CT (Logistic regression: p = 0.04). Co-variates as smoking habits, age, drug exposure (chemotherapy, tamoxifen, herceptin) did not influence the outcome on multi-variate analysis.ConclusionsThe use of dose-volume constraints significantly reduced post-RT radiological changes on X-ray in LRRT for BC. The lung changes on CT were generally limited when this strategy was used and could not always be picked up on chest X-ray. Variation in dosimetry alone was correlated with occurrence of lung changes on CT. Purpose/Objective(s)It is well known that LRRT for BC is associated with pulmonary radiological changes. We studied post-RT lung changes on X-ray and CT and correlated the findings with common dosimetric factors and co-variates, and compared the outcome with a previously reported cohort of 137 irradiated women. It is well known that LRRT for BC is associated with pulmonary radiological changes. We studied post-RT lung changes on X-ray and CT and correlated the findings with common dosimetric factors and co-variates, and compared the outcome with a previously reported cohort of 137 irradiated women. Materials/Methods88 women underwent chest X-ray and CT pre- and 4 months after 3-D planned LRRT aimed at maximizing the dose to the ipsilateral lung to V20 < 30%. The lung field was divided in 3 sections and density changes were graded (0-3). Patients with radiological changes were compared with non-responders. Data on clinically important patient- and treatment-related co-variates were gathered prospectively and correlated with post-RT lung changes, as was dosimetric factors (V13, V20, V30 and mean dose). 88 women underwent chest X-ray and CT pre- and 4 months after 3-D planned LRRT aimed at maximizing the dose to the ipsilateral lung to V20 < 30%. The lung field was divided in 3 sections and density changes were graded (0-3). Patients with radiological changes were compared with non-responders. Data on clinically important patient- and treatment-related co-variates were gathered prospectively and correlated with post-RT lung changes, as was dosimetric factors (V13, V20, V30 and mean dose). ResultsThe use of dose-volume constraints significantly reduced moderate-severe radiological changes on X-ray compared with the earlier treatment series (Chi square trend test: p < 0.001). Symptomatic pneumonitis was also very rare in the present study. There was no agreement on CT and X-ray as diagnostic tools for post-RT pneumonitis. V13 was most strongly and independently correlated with radiological changes on CT (Logistic regression: p = 0.04). Co-variates as smoking habits, age, drug exposure (chemotherapy, tamoxifen, herceptin) did not influence the outcome on multi-variate analysis. The use of dose-volume constraints significantly reduced moderate-severe radiological changes on X-ray compared with the earlier treatment series (Chi square trend test: p < 0.001). Symptomatic pneumonitis was also very rare in the present study. There was no agreement on CT and X-ray as diagnostic tools for post-RT pneumonitis. V13 was most strongly and independently correlated with radiological changes on CT (Logistic regression: p = 0.04). Co-variates as smoking habits, age, drug exposure (chemotherapy, tamoxifen, herceptin) did not influence the outcome on multi-variate analysis. ConclusionsThe use of dose-volume constraints significantly reduced post-RT radiological changes on X-ray in LRRT for BC. The lung changes on CT were generally limited when this strategy was used and could not always be picked up on chest X-ray. Variation in dosimetry alone was correlated with occurrence of lung changes on CT. The use of dose-volume constraints significantly reduced post-RT radiological changes on X-ray in LRRT for BC. The lung changes on CT were generally limited when this strategy was used and could not always be picked up on chest X-ray. Variation in dosimetry alone was correlated with occurrence of lung changes on CT.

Retrospective analysis of 119 Chinese noninflammatory locally advanced breast cancer cases treated with intravenous combination of vinorelbine and epirubicin as a neoadjuvant chemotherapy: a median follow-up of 63.4 months

BackgroundThis study is a retrospective evaluation of the efficacy of neoadjuvant chemotherapy (NC) with a vinorelbine (V) and epirubicin (E) intravenous combination regimen and is aimed at identification of predictive markers for the long-term outcome in noninflammatory locally advanced breast cancer (NLABC).MethodsOne-hundred-and-nineteen patients with NLABC were identified from September 2001 to May 2006. Analysis was performed in March 2008, with a median follow-up of 63.4 months (range, 9-76 months). All patients were diagnosed with invasive breast cancer using 14 G core needle biopsy and treated with three cycles of VE before surgery. Local-regional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonal therapy according to hormone receptor status. Tissue sections cut from formalin-fixed paraffin-embedded blocks from biopsy specimens and postoperative tumor tissues were stained for the presence of estrogen receptor (ER), progesterone receptor (PgR), HER-2 (human epidermal growth factor receptor-2), and MIB-1(Ki-67).ResultsPatients characteristics were median age 52 years (range: 25-70 years); clinical TNM stage, stage IIB (n = 32), stage IIIA (n = 56), stage IIIB (n = 22) and stage IIIC (n = 9). All patients were evaluable for response: clinically complete response was documented in 27 patients (22.7%); 78 (65.6%) obtained partial response; stable disease was observed in 13 (10.9%); 1 patient (0.8%) had progressive disease. Pathological complete response was found in 22 cases (18.5%). Seventy-five patients were alive with no recurrence after a median follow-up of 63.4 months, the 5-year rates for disease-free survival and overall survival were 58.7% and 71.3%, respectively, after the start of NC. On multivariate analysis, the independent variables associated with increased risk of relapse and death were high pre-Ki-67(p = 0.012, p = 0.017, respectively), high post-Ki-67 expression (p = 0.045, p = 0.001, respectively), and non-pCR (p = 0.034, p = 0.027, respectively). A significantly increased risk of death was associated with lack of pre-ER expression (p = 0.002). Among patients with non-pCR, those with a pathological response at the tumor site with special involvement (i.e. skin, vessel and more than one quadrant) were at a higher risk of disease relapse and death (p < 0.001, p = 0.001, respectively).ConclusionThis study suggests the promising use of a VE regimen as NC for Chinese NLABC after a median follow-up of 63.4 months. Pathological response in the tumor site, pre-Ki-67 and post-Ki-67 expression, and pre-ER expression were the important variables that predicted long-term outcome. Patients with pathological special involvement at the primary site after NC had the lowest survival rates.

Impact of High-Dose Chemotherapy on the Ability to Deliver Subsequent Local–Regional Radiotherapy for Breast Cancer: Analysis of Cancer and Leukemia Group B Protocol 9082

To report, from Cancer and Leukemia Group B Protocol 9082, the impact of high-dose cyclophosphamide, cisplatin, and BCNU (HD-CPB) vs. intermediate-dose CPB (ID-CPB) on the ability to start and complete the planned course of local-regional radiotherapy (RT) for women with breast cancer involving >or=10 axillary nodes. From 1991 to 1998, 785 patients were randomized. The HD-CPB and ID-CPB arms were balanced regarding patient characteristics. The HD-CPB and ID-CPB arms were compared on the probability of RT initiation, interruption, modification, or incompleteness. The impact of clinical variables and interactions between variables were also assessed. Radiotherapy was initiated in 82% (325 of 394) of HD-CPB vs. 92% (360 of 391) of ID-CPB patients (p = 0.001). On multivariate analyses, RT was less likely given to patients who were randomized to HD treatment (odds ratio [OR] = 0 .38, p < 0.001), older (p = 0.005), African American (p = 0.003), postmastectomy (p = 0.02), or estrogen receptor positive (p = 0.03). High-dose treatment had a higher rate of RT interruption (21% vs. 12%, p = 0.001, OR = 2.05), modification (29% vs. 14%, p = 0.001, OR = 2.46), and early termination of RT (9% vs. 2%, p = 0.0001, OR = 5.35), compared with ID. Treatment arm significantly related to initiation, interruption, modification, and early termination of RT. Patients randomized to HD-CPB were less likely to initiate RT, and of those who did, they were more likely to have RT interrupted, modified, and terminated earlier than those randomized to ID-CPB. The observed lower incidence of RT usage in African Americans vs. non-African Americans warrants further study.

Study on predictors of long term results for neo-adjuvant chemotherapy in locally advanced breast cancer

To identify predictive markers of the long-term outcome for neo-adjuvant chemotherapy (NC) in locally advanced breast cancer (LABC) treated with intravenous vinorelbine (V) and epirubicin (E) combination regimen. One hundred and nineteen patients with LABC were treated from September 2001 to May 2006. All patients were diagnosed as invasive breast cancer by 14G core needle biopsy and treated with three cycles of VE regimen before the operation. The patients were subjected to surgery and subsequently were given other three cycles of VE or cyclophosphamide+epirubicin+fluorouracil (CEF) regimen according to the clinical responses. Local-regional radiotherapy was applied to all patients after the chemotherapy and followed by hormone-therapy according to hormone receptor status. The impact of clinical, pathological, and immunohistochemical features on disease free survival (DFS) and overall survival (OS) was evaluated. All patients were evaluable for responses: clinical complete response was documented in 27 patients (22.7%), 78 patients (65.5%) obtained partial clinical response. The pathological complete response was found in 22 cases (18.5%). Of the patients, 115 cases (96.6%) were followed-up for a median time of 63.4 months (range, 9-76 months), the 5-year DFS rate and OS rate was 58.7% and 71.3%, respectively. On multivariate analysis, high pre-Ki-67 (P=0.012) and post-Ki-67 expression (P=0.045), no pathological complete response after NC (P=0.034) were associated with the higher risk of disease relapse; high pre-Ki-67 (P=0.017) and post-Ki-67 expression (P=0.001), negative pre-ER (P=0.002) and no pathological complete response after NC (P=0.034) were associated with a shorter survival. Pathological response in primary tumor, pre-Ki-67 and post-Ki-67 expression, pre-ER expression are important predictors of long-term outcome for LABC patients with three cycles of VE regimen before operation.

Randomized study testing as adjuvant chemotherapy the same primary (neoadjuvant) epirubicin/vinorelbine (EN) regimen versus docetaxel (TXT) in inflammatory breast cancer (IBC)

590 Background: The multimodal approach of IBC resulted in improved survival but the IBC still remains the most aggressive form of breast cancer. The endpoints of the study were to a) evaluate the efficacy and safety of primary chemotherapy (EN), b) evaluate a better chemotherapy sequence (primary and adjuvant), and c) analyze the predictive value and changes of some biomarkers (ER, PR, Ki67 and HER2 status) in IBC. Methods: From 4/2002 to 10/2007, 56 patients with IBC entered the study. The molecular markers were obtained from tumor specimens before chemotherapy by biopsy and surgery after. After diagnosis the pts were randomized to the following sequence: EN (E 120 mg/m2 d 1 plus N 25 mg/m2 d 1 & 8) x 4 cycles -> surgery or radiotherapy -> adjuvant TXT (100 mg/m2) x 4 cycles (Group A) or EN x 4 cycles (Group B), all regimens q 3 wks. After adjuvant therapy all pts received RT and endocrine therapy in ER/PgR+ tumors. From 6/2006 the pts with HER2+ status also received trastuzumab adjuvant x 1 yr. The characteristics of the evaluable pts (28 group A and 26 group B) were well balanced between the groups (A/B): median age (53/53.5 yrs), premenopausal (12/10 pts), ER- (15/15 pts), PgR- (15/17), and HER2+ (20/21). Results: Also the overall clinical objective responses to induction chemotherapy were well balanced between group A vs. B: 89% vs. 85%. One patient in group A and 3 pts in group B underwent local-regional radiotherapy instead of surgery. The pathologic objective responses between group A vs. B were: cCR (7 vs. 11%) and cPR (82 vs. 73%). At median 36 months of follow-up, we observed 10 vs. 16 relapses and 3 vs. 9 deaths. Both sequential chemotherapies were manageable, feasible and well tolerated. One patient showed an anaphylactic reaction to TXT after the first cycle. Better results in group A with 5yrs DFS odds ratio rates 0.50 (95%CI 1.1–0.3, p 0.8), and OS odds ratio 0.30 (95% CI 1.0–01, p.06). Conclusions: The data suggest that the sequential use of two non- cross resistance chemotherapy schedules is well tolerated, active and feasible. This monocentric study demonstrates for the first time an improvement of the principal survival endpoints by means of an adjuvant regimen different from the primary one. No significant financial relationships to disclose.

Quantitative assessment of lung density changes after 3-D radiotherapy for breast cancer

Our aim was to reduce the rates of clinical and radiological pneumonitis in local-regional radiotherapy (RT) for breast cancer compared to a previous treatment series by applying a pre-planned lung dose volume constraint. 3-D dose planning was performed in 66 women with the aim of not exceeding an ipsilateral V20 of 30%. The patients were followed for short-term signs/symptoms of post-RT pneumonitis and radiological changes on chest CT 4 months after RT. Radiological abnormalities were scored with a CT-adapted modification of a semi-quantitative classification system originally proposed by Arriagada which accounts for severity and affected lung regions. The abnormal subvolumes were contoured and the mean doses were calculated. Three cases of mild and one case of moderate symptomatic pneumonitis were diagnosed. The mean V20 was higher in symptomatic than in unaffected patients, 29% vs. 24% (p =0.04). Mild/moderate radiological changes were frequently observed on CT in regions with average doses >30 Gy. According to multivariate modeling, a trend for association was found between the studied dosimetric factors V13, V20, V30 and mean lung dose, and moderate-severe changes on CT but not with patient specific covariates, e.g. chemotherapy or tamoxifen exposure. 3-D planned local-regional RT with a preplanned lung dose volume constraint of V20 <30% resulted in few cases of moderate symptomatic pneumonitis. Mild/moderate radiological changes were still detectable on CT in subvolumes receiving doses >30 Gy. Long-term follow-up for evaluation of possible late morbidity is warranted.

Body Mass Index Predicts the Incidence of Radiation Pneumonitis in Breast Cancer Patients

In patients receiving breast radiotherapy, the risk of radiation pneumonitis has been associated with the volume of irradiated lung, and concomitant methotrexate, paclitaxel, and tamoxifen therapy. Many of the studies of radiation pneumonitis are based on estimates of pulmonary risk using central lung distance that is calculated using two-dimensional techniques. With the treatment of internal mammary nodes and three-dimensional treatment planning for breast cancer becoming increasingly more common, there is a need to further consider the impact of dose-volume metrics in assessing radiation pneumonitis risk. We herein present a case control study assessing the impact of clinical and dose-volume metrics on the development of radiation pneumonitis in patients receiving sequential chemotherapy and local-regional radiotherapy.