Locoregional Radiotherapy Research Articles

Submerged goiter proven to be metastatic infiltration of a neuro-endocrine Merkel cell carcinoma

BackgroundMerkel cell carcinoma (MCC) is an uncommon neuroendocrine cutaneous carcinoma. Metastases to the thyroid gland are rare and may present diagnostic difficulties.Case presentationA 73-year-old woman presented with a hard mass in the adipose tissue of the right inguinal area. This mass was surgically excised and the histology examination showed the existence of a MCC. CT scans revealed a sizable lesion with imaging features of a submerged goiter, invasive to the upper mediastinum. The patient received chemotherapy following by locoregional radiotherapy at the bed of the excised lesion. During the next 10 months the patient was asymptomatic, serum markers values were normal and CT scans findings were stable. However, afterwards NSE and chromogranin values raised and CT scans revealed an enlargement of the submerged goiter. The patient became symptomatic, mainly experiencing respiratory inconvenience. Surgical excision of the right lobe of the thyroid gland was decided and performed without any complications. The histopathology examination showed infiltration of the thyroid gland by a neuroendocrine carcinoma with characteristics compatible with MCC.ConclusionsThe rare case of metastatic infiltration of the thyroid gland by a MCC based on histological and immunohistochemical findings was described. This case report is of clinical significance indicating that by any abnormal finding in the thyroid gland in patients with a malignant disease, the diagnostic approach should always contain consideration of metastasis from the primary tumor.

PO-0699: Impact of locoregional treatment on survival in patients presented with metastatic breast carcinoma

Objectives: In this study, we tried to evaluate the efficacy of locoregional treatment (LRT) in patients with metastatic breast carcinoma (MBC). Materials and methods: The medical records of 227 patients with MBC at initial presentation between April 1999 and January 2013 were retrospectively evaluated. The median age at diagnosis was 50 years (range, 27e83 years). Thirty-nine patients (17%) had no LRT. Among patients who had LRT, 2 (1%) had locoregional radiotherapy (RT) alone, 54 (29%) had surgery alone [mastectomy, n ¼ 50; breast conserving surgery (BCS), n ¼ 4] and 132 (70%) had surgery (mastectomy, n ¼ 119; BCS, n ¼ 13) followed by locoregional RT. Results: The median follow-up time was 35 months (range, 4e149 months). Five-year OS and PFS rates were 44% and 20%, respectively. In both univariate and multivariate analysis LRT per se did not affect OS and PFS rates. However, the 5-year OS and PFS rates were significantly higher in patients treated with locoregional RT than the ones who were not. The corresponding rates were 56% vs. 24% for OS and 27% vs. 7% for PFS (p < 0.001). Median survival was 67 months and 37 months, respectively. Conclusion: Our study showed that patients with MBC who received postoperative locoregional RT may have a survival advantage compared with patients who were only treated by surgery. A phase III trial testing the role of adjuvant locoregional RT may help to distinguish patients who will benefit from adjuvant RT.

Clinical and computed tomography features of adult abdominopelvic desmoplastic small round cell tumor

To investigate the clinical and computed tomography (CT) features of desmoplastic small round cell tumor (DSRCT), we retrospectively analyzed the clinical presentations, treatment and outcome, as well as CT manifestations of four cases of DSRCT confirmed by surgery and pathology. The CT manifestations of DSRCT were as follows: (1) multiple soft-tissue masses or diffuse peritoneal thickening in the abdomen and pelvis, with the dominant mass usually located in the pelvic cavity; (2) masses without an apparent organ-based primary site; (3) mild to moderate homogeneous or heterogeneous enhancement in solid area on enhanced CT; and (4) secondary manifestations, such as ascites, hepatic metastases, lymphadenopathy, hydronephrosis and hydroureter. The prognosis and overall survival rates were generally poor. Commonly used treatment strategies including aggressive tumor resection, polychemotherapy, and radiotherapy, showed various therapeutic effects. CT of DSRCT shows characteristic features that are helpful in diagnosis. Early discovery and complete resection, coupled with postoperative adjuvant chemotherapy, are important for prognosis of DSRCT. Whole abdominopelvic rather than locoregional radiotherapy is more effective for unresectable DSRCT.

Radiothérapie mammaire locorégionale et traitement concomitant par trastuzumab

The overexpression of the Human Epidermal Growth Factor Receptor 2 (HER2) is observed in 15 % of breast cancers and associated with poor prognosis in terms of overall survival. Trastuzumab is an anti-HER2 targeted therapy, leading to a specific inhibition of the molecular mechanisms triggered by this receptor. In an adjuvant setting, trastuzumab and radiotherapy have each proved their oncologic efficacy in the management of the breast tumours presenting this molecular profile. However, both treatments expose to an increased risk of toxicities, particularly cardiovascular ones. Moreover, the radiosensitizing effect of trastuzumab has been proved in vitro and in vivo. Hence, in clinical practice, the benefit/risk ratio of a concurrent treatment remains to be defined.This literature review has for purposes to describe the rationale making conceivable the administration of trastuzumab concurrently with locoregional breast radiotherapy, and to remind the results of the clinical studies having assessed this therapeutic association.

繰り返す局所治療で長期生存した腹部大動脈・頸部リンパ節再発胃癌の1例

繰り返す局所治療で長期生存した腹部大動脈・頸部リンパ節再発胃癌の1例

Leptomeningeal dissemination in gall bladder carcinoma: sequelae of long-term survival?

Patients with gall bladder malignancies usually present at an advanced stage with less than 20% cases being resectable at presentation and over a half harbouring distant metastases to liver or paraaortic nodes. Long-term cure is uncommon and so is the presence of central nervous system metastases. We present the case of a middle-aged woman with adenocarcinoma gall bladder, treated with postoperative locoregional irradiation following simple cholecystectomy, who developed headache, backache, vision loss, and multiple joint pains six years following adjuvant therapy. A diagnosis of leptomeningeal carcinomatous meningitis was established with cerebrospinal fluid cytology positivity for carcinoma. She deteriorated on palliative cranial irradiation and was managed with best supportive care.

EP-1560: Potential role of VMAT and DIBH in the locoregional irradiation of left breast cancer.

EP-1560: Potential role of VMAT and DIBH in the locoregional irradiation of left breast cancer.

EP-1590: Is IMRT superior to 3D-CRT for post-mastectomy loco-regional irradiation? An in silico comparative planning study

EP-1590: Is IMRT superior to 3D-CRT for post-mastectomy loco-regional irradiation? An in silico comparative planning study

Post-mastectomy radiation beyond chest wall in patients with N1 breast cancer: is there a benefit?

Nodal stage is the most important prognostic factor and one of the indicators for loco-regional radiation in patients with breast cancer. N1 (patients with 1-3 lymph node metastases in axilla) nodal stage is a controversial area as far as axillary and supraclavicular fossa (SCF) irradiation is concerned. We conducted a retrospective analysis at our institute to assess the impact of post-mastectomy radiotherapy (PMRT) beyond chest wall (CW) in N1- nodal stage breast cancer patients. Since January 2004 to December 2007, 293 post-mastectomy patients with N1 nodal stage breast cancer were analyzed for patient-related characteristics such as age, menopausal status, pathological stage/tumour size, tumour location, histology, oestrogen/progesterone receptor status, histological grade, extra capsular extension, lymph vascular invasion and treatment-related factors, PMRT and systemic therapy. Outcome studied were locoregional recurrence rate (LRR), disease free survival (DFS) and overall survival (OS). At a median follow up of 55m, 260 patients received radiotherapy; 212 to CW+SCF, 48 to the CW only; and 33 patients did not receive radiotherapy. LRR was 5% in patients who received radiotherapy to CW+SCF and 8% in CW only (P = 0.34). There was no difference in the DFS between the two groups. OS at 5 year was 88% in CW+SCF group and 76% in CW only group respectively (P < 0.001). In N1 nodal stage patients with breast cancer LRR was not significantly different after radiation to CW+SCF or to the CW only but OS was significantly better.

Locoregional Radiotherapy in Patients With Breast Cancer Responding to Neoadjuvant Chemotherapy: A Paradigm for Treatment Individualization

The increasing use of neoadjuvant chemotherapy for patients with breast cancer with axillary nodal metastases has created debate among multidisciplinary tumor boards centered on the optimal use of locoregional radiotherapy. Clinical decision making regarding the use of postmastectomy and regional nodal radiotherapy has been built on evidence from numerous randomized clinical trials where pathologic staging from upfront surgery was the determinant of receiving treatment after adjuvant chemotherapy. It is generally recommended that patients who have axillary nodal metastases receive radiotherapy to the chest wall and regional nodes after mastectomy or to breast and regional nodes after lumpectomy. Conversely, in patients with negative axillary nodes, radiotherapy is not typically recommended after mastectomy and is confined to the breast alone after lumpectomy. The absence of similar evidence in the setting of neoadjuvant chemotherapy has led to conflicting opinions about the key factors that should drive the clinical decision to administer locoregional radiotherapy. The thoughtful concepts of Marks and Prosnitz endorse the concept that the prechemotherapy-positive axillary nodal metastases are the key factor and caution that reducing radiotherapy based on chemotherapy response places women at risk for worse breast cancer mortality. Conversely, others have supported the idea that pathologic nodal status postchemotherapy is the important factor and argued that for patients who become pathologically node negative after neoadjuvant chemotherapy, radiotherapy may not offer significant benefit. It is clear that the absence of evidence permits the generation of disparate treatment recommendations for the same clinical scenario, placing women at risk for either overor undertreatment. As stated by Marks and Prosnitz, the critical threat of suboptimal locoregional cancer treatment is that it will result in worse breast cancer survival. Significant evidence exists that the addition of locoregional radiotherapy after upfront surgery and adjuvant chemotherapy can improve breast cancer survival in addition to providing large gains in locoregional cancer control. The Early Breast Cancer Trialists Collaborative Group (EBCTCG) 2005 meta-analysis studied the effect of radiotherapy on locoregional recurrence at 5 years and breast cancer mortality at 15 years. This demonstrated that the absolute benefit in reducing breast cancer mortality resulting from radiotherapy was related to the magnitude of locoregional risk in the nonirradiated patients. However, an analysis that divided absolute locoregional recurrence risk reduction after lumpectomy or mastectomy by 5 years into three categories of 10%, 10% to 20%, or 20% demonstrated that for those with 10% absolute reduction in local recurrence resulting from radiotherapy by 5 years, there was no improvement in breast cancer mortality by 15 years. Similarly, the EBCTCG 2011 meta-analysis demonstrated that the reductions gained in 10-year overall breast cancer recurrence rate (local, regional, and distant) by postlumpectomy breast radiotherapy resulted in improvement in 15year breast cancer mortality rate. An analysis that stratified the predicted absolute reduction in 10-year overall breast cancer recurrence risk from radiotherapy into groups of low ( 10%), intermediate (10% to 19%), and large ( 20%) found in the low-risk group an absolute reduction of 6.9% with radiotherapy (18.9% without v 12% with radiotherapy), corresponding to a negligible absolute reduction in 15-year risk of death resulting from breast cancer of 0.1% ( 7.5% to 7.7%). Collectively these analyses support that the survival benefit from radiotherapy after upfront surgery and chemotherapy is related to an individualpatient’sriskofanyrecurrencebasedonclinicalandpathologic features. It is recognized that the extent of response to neoadjuvant chemotherapy is associated with prognosis, with the best relative disease-free survival occurring in those who achieve a complete pathologic response. Therefore, it is logical that if upfront chemotherapy can place a patient in a sufficiently low risk category for locoregional recurrence after surgery, then adding radiotherapy will not significantly reduce the risk of breast cancer mortality. There is supporting evidence that neoadjuvant chemotherapy response is linked to lower rates of subsequent locoregional recurrence risk in the absence of radiotherapy. Mamounas et al analyzed locoregional recurrence rates in approximately 3,000 women enrolled onto two National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials evaluating neoadjuvant chemotherapy (NSABP B-18 and NSABP B-27). Both protocols specified that patients treated with lumpectomy were required to receive breast radiotherapy only, and patients treated with mastectomy were not allowed to receive any radiotherapy. The combined analysis of these two trials provides important information on the rates, patterns, and independent predictors of locoregional recurrence after neoadjuvant chemotherapy. The 10-year cumulative incidence of locoregional recurrence was 12.3% for patients who underwent mastectomy (local, 8.9%; regional, 3.4%) JOURNAL OF CLINICAL ONCOLOGY COMMENTS AND CONTROVERSIES VOLUME 32 NUMBER 6 FEBRUARY 2

Abstract CS01-1: The role of pathological staging of the axilla and sentinel lymph node biopsy before versus after neoadjuvant chemotherapy

Abstract Neoadjuvant (neo) chemotherapy (CTX) is standard of care for managing pts that present with locally advanced/inoperable breast cancer. This strategy is also routinely offered to women whose cancers are resectable but where primary tumor downstaging is expected to improve lumpectomy eligibility and cosmesis. In the latter scenario it must be clear that CTX is an indicated component of the multidisciplinary care, so that risk of over-treatment is minimized. For many pts, the value of CTX is documented by the size and molecular marker status of the primary invasive tumor. In others, the value of CTX will be confirmed by histopathologic evidence of metastatic disease in the axillary nodal basin, established by either percutaneous needle biopsy or sentinel lymph node (SLN) biopsy. Once the decision has been made to pursue neoCTX, the multidisciplinary treatment team should be proactive in designing the management algorithm for the axilla, and this plan should address the pre- as well as post-neoCTX phases. These decisions can have important implications with regard to prognostic value, treatment planning, and surgical morbidity. Reconciling the desires to minimize treatment toxicity while maximizing disease control and information regarding tumor biology can be quite challenging. The accuracy of SLN biopsy prior to delivery of CTX is well-established. The SLN is clearly more definitive than axillary ultrasound and image-guided FNA biopsy, where the false negative rates approach 20%. Pts that undergo a pre-CTX SLN biopsy documenting node- negative disease are clearly in an advantageous position- these pts can proceed onto neoCTX followed by breast-only surgery/radiation. The major downside to this approach is the need for coordinating the pre-treatment surgical plan. The algorithm becomes more complex when the neoCTX pt has documented node-positive disease (established via FNA or SLN). For these pts, it is presently unclear whether a completion axillary lymph node dissection (ALND) is always necessary in conjunction with the breast surgery following delivery of the CTX. If clinically-evident axillary disease persists, then ALND will be therapeutic in regional control of disease. If however, the axillary disease appears to have been down-staged, then the value of the completion ALND is less clear. NeoCTX can completely clear nodal metastases in 25% of cases, and in up to half of node-positive breast cancer the initial/pretreatment SLN biopsy will have resected the only metastatic nodes present in the axilla. In this scenario, the completion ALND and documenting the presence versus absence of post-treatment residual disease primarily serves the purpose of providing prognostic value, and potentially affects loco regional radiation planning. Whether or not regional XRT should be routinely offered in lieu of the completion ALND is a subject of ongoing debate. Another option is to perform post-treatment SLN biopsy for definitive assessment of chemosensitivity in cases of initially node-positive disease, with the hope that a negative post-treatment SLN biopsy can obviate the need for ALND, however single-institution retrospective studies as well as prospective clinical trials (ACOSOG Z1071) have revealed broad variation in accuracy, with SLN false negative rates ranging from 10-40%. Finally, it has been suggested by many clinicians that neoCTX pts should undergo SLN biopsy following completion of the CTX (concomitantly with their breast surgery) without any up-front axillary staging. This approach avoids multiple exposures to general anesthesia and minimizes likelihood of the pt facing the longterm ALND morbidity. On the other hand, this approach is still fraught with the uncertainty of SLN accuracy related to treatment effects on the false negative rates. Furthermore, this strategy eliminates the possibility of differentiating the pts who presented with node-negative disease from those who were actually node-positive at diagnosis but whose disease was down staged by the neoCTX. It can be argued that this distinction has relevant implications regarding prognosis and benefits of regional XRT. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr CS01-1.

Abstract P5-14-11: Locoregional toxicities after adjuvant radiotherapy with or without concurrent bevacizumab in patients with non-metastatic breast cancer

Abstract Purpose/Objectives Few data are available regarding the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (RT) in breast cancer, especially in terms of late toxicity. The aim of this study was to determine early and late loco-regional toxicities among patients with non-metastatic breast cancer treated with this combination. Materials/Methods In our prospective and descriptive study, we analyzed loco-regional toxicities of adjuvant RT in patients with non-metastatic breast cancer receiving either concurrent bevacizumab or not in the randomized trial BEATRICE. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events (v3.0). Evaluation was done during RT and 12 months after the end of RT. All patients provided written informed consent before enrollment. Statistical analysis was performed to analyze toxicity between the two groups. Results From September 2007 to July 2009, we included 84 patients from the randomized trial BEATRICE which evaluate the efficacy and safety of the addition of bevacizumab to standard adjuvant therapy in patients with triple negative breast cancer; 39 women received an adjuvant RT with concurrent bevacizumab and 45 women received an adjuvant RT alone. Evaluation at 12 months was available for all the patients. All patients had a triple negative non-metastatic breast cancer and had an adjuvant chemotherapy then RT. Among patients receiving concurrent bevacizumab with RT, a total of 35 patients (90%) achieved a whole breast irradiation (median dose: 50 Gy) with a boost in the surgical bed (median dose: 16 Gy) and 4 patients (10%) had a post mastectomy RT (median dose 50 Gy); lymph node RT was performed in 19 patients (49%) with internal mammary chain RT in 12 patients (31%). Mean time of bevacizumab treatment was 11.7 months [2.1-12.6] and mean total dose of bevacizumab was 15000 mg [3330-28080]. Among patients receiving RT alone, 38 patients (84%) achieved a whole breast irradiation (median dose: 50 Gy) with a boost in the surgical bed (median dose: 16 Gy) and 7 patients (16%) had a post mastectomy RT (median dose 50 Gy); lymph node RT was performed in 21 patients (47%) with internal mammary chain RT in 14 patients (31%). Radiation treatment parameters were not significantly different between the two groups. Incidence of acute grade 3 dermatitis was 10% in patients receiving bevacizumab associated with RT and 6% in patients receiving RT alone without significant difference. One year after the end of RT, the most common late toxicities in the group receiving bevacizumab and RT were grade 1-2 pain (18%), grade 1-2 fibrosis (8%), grade 1-2 arm lymphedema (8%) and grade 1-2 telangiectasia (6%).There was no significant difference in pain, radiation fibrosis, telangiectasia, arm lymphedema and dyspnea between the two groups. No patient experienced grade 3-4 toxicity in the two groups. Conclusions Our results indicate that concurrent bevacizumab with loco-regional RT provide acceptable early and late toxicities after one year in patients with non-metastatic breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-11.

Abstract P1-13-14: Discordance of ER and PR status between primary and recurrent breast cancer in association with endocrine therapy

Abstract Background: Discordance in tumor receptor status between primary and recurrent tumors has been previously reported. Discordant ER/PR status has been used to differentiate recurrences from new primaries. We evaluated discordance rates of ER and PR expression between the primary and locoregional/contralateral recurrences and examined the relationship with adjuvant endocrine therapy (ET). Methods: We conducted a retrospective chart review of breast cancer patients (pts) treated with lumpectomy and adjuvant locoregional radiation (RT) from 1999-2005 at the Princess Margaret Cancer Centre. Tumor recurrence was classified as locoregional recurrence (LRR) for ipsilateral breast or lymph node recurrence, contralateral disease (CD) or distant recurrence. ER and PR were assessed by immunohistochemistry; positive if &amp;gt;10% tumor cells staining, borderline if 10% staining, and negative if &amp;lt;10% staining. Univariate analyses were applied to determine the association of receptor discordance with age, menopausal status, tumor grade, endocrine therapy or adjuvant chemotherapy. Results: All 441 pts had a lumpectomy with negative margins and RT, and had a median follow-up of 8.3 years. The median age at primary surgery was 57, and 67% of pts were postmenopausal. ET (tamoxifen and/or aromatase inhibitors) was initiated in 294 (84%) eligible patients. There were 24 (5.4%) pts with LRR, 20 (4.5%) pts with CD, and 28 (6.3%) with distant metastases. Nine pts with LRR also had distant disease, and 3 pts with CD also had distant disease. Among pts with LRR, 17 had ER/PR status available for comparison. Discordance rates for ER and PR were (1/17) 5.9% and (3/17) 17.6%, respectively, and the most common change was ER becoming positive, and PR becoming negative (75%). For pts with CD, 18 had ER/PR status available for comparison. Discordance rates for ER and PR were (7/18) 38.9% and (9/18) 50%, respectively. The most common change was ER becoming positive (86%), and PR becoming positive (75%). Distant disease receptor status was only available for two patients, therefore not included. The patient with LRR and discordant ER did not receive ET, while pts with LRR and discordant PR all received ET. Among patients with CD, 15% of patients with discordant ER status received ET, and 33% with discordant PR received ET. There was no statistically significant association between discordance rates in either LRR or CD groups and use of ET. Similarly, discordance rates were not associated with the other patient or tumor variables studied, or the development of distant metastases or death. Conclusions: Discordance of ER and PR expression was low in LRR and higher in CD, where the majority of changes were from negative to positive receptor status. Receptor discordance was not associated with endocrine therapy. This study suggests that the biology of LRR and CD may be different, and re-evaluation of receptor status could lead to additional treatment options becoming available from an endocrine standpoint. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-13-14.

Résultats préliminaires d’une tomothérapie hélicoïdale adjuvante avec boost intégré dans le cadre d’un traitement conservateur d’un cancer du sein

PurposeTo evaluate the dosimetry and acute toxicity of helical tomotherapy for locoregional irradiation of patients after breast-conserving surgery. Patients and methodsTwenty breast cancer patients with breast-conserving surgery treated by helical tomotherapy have been studied. The median age was 49 (min: 25, max: 69). The whole breast, tumour bed and lymph nodes were prescribed 52.2Gy, 63.8Gy and 50.4Gy, all in 29 fractions. The dose per fraction was 2.2Gy to the boost, 1.8Gy to the breast and 1.74Gy to the lymph node volumes. The reproducibility was analysed by recording the daily shifts in x, y and z directions and roll rotation. All toxicities were described using the Common Terminology Criteria for Adverse Effects v3.0. ResultsTwenty-two tumours were irradiated. Six-eight percent were located in the inner quadrant. In 90 % of patients supraclavicular and internal mammary nodes were treated. The coverage of planning target volumes (PTV) was as follows: PTV boost: V107=0.3 %±0.5 SD, V95=98.4 %±1.9 SD; PTV breast: −V107=7.8 %±17.3 SD, V95=96.8 %±2.2 SD; PTV LN: V107=2.5 %±4.2 SD, V95=92.7 %±13.2 SD. The mean V20 of the homolateral lung was 18.9 %±3.5 SD. For left side lesion, the mean V30 of the heart was 0.9 %±0.8 SD. The mean V5 was: V5 homolateral lung: 73.1 %±11.8 ET, controlateral lung: 38.9 %±21, heart (left side breast): 57.3 %±21, controlateral breast: 15.5 %±9.6. Median shifts were as follow: x-axis –0.04mm (IC 95: –0.4 +0.38), y-axis –0.37mm±5.51 (IC 95: –0.88 +0.14), z-axis 2.90mm±5.42 (IC 95:+2.4+3.4) and roll rotation 0.22±1.10 (IC 95: –0.1+0.32). The treatment tolerance was acceptable with 1 definitive interruption couple of fractions before the end and 3 temporal interruptions for skin toxicity. No grade 3 or 4 toxicity. Ninety-five percent of patients experienced skin toxicity: 45 % grade 2. There were 3 cases of oesophagitis. The median follow-up of presented series is 9.7 months and all of the patients are free of disease without any residual early or late toxicity. ConclusionsHelical tomotherapy can achieve full target coverage while protected to the heart and ipsilateral lung. This treatment was well tolerated and reproducible. However, the low doses to normal tissue volumes need to be reduced in future studies.

Primary testicular lymphoma

Primary testicular lymphoma (PTL) is a rare, clinically aggressive form of extranodal lymphoma. The vast majority of cases are histologically diffuse large B-cell lymphoma, but rarer subtypes are clinically important and must be recognized. In this review, we discuss the incidence, clinical presentation, and prognostic factors of PTL and present a summary of the recent advances in our understanding of its pathophysiology, which may account for the characteristic clinical features. Although outcomes for patients with PTL have historically been poor, significant gains have been made with the successive addition of radiotherapy (RT), full-course anthracycline-based chemotherapy, rituximab and central nervous system-directed prophylaxis. We describe the larger retrospective series and prospective clinical trials and critically examine the role of RT. Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given every 21 days with intrathecal methotrexate and locoregional RT is the current international standard of care, a substantial minority of patients progress, representing an unmet medical need. Finally, we discuss new treatment approaches and recent discoveries that may translate into improved outcomes for patients with PTL.

Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis

Systemic chemotherapy is the basic palliative treatment for metastatic nasopharyngeal carcinoma (NPC); however, it is not known whether locoregional radiotherapy targeting the primary tumor and regional lymph nodes affects the survival of patients with metastatic NPC. Therefore, we aimed to retrospectively evaluate the benefits of locoregional radiotherapy. A total of 408 patients with metastatic NPC were included in this study. The mortality risks of the patients undergoing supportive treatment and those undergoing chemotherapy were compared with that of patients undergoing locoregional radiotherapy delivered alone or in combination with chemotherapy. Univariate and multivariate analyses were conducted. The contributions of independent factors were assessed after adjustment for covariates with significant prognostic associations (P < 0.05). Both locoregional radiotherapy and systemic chemotherapy were identified as significant independent prognostic factors of overall survival (OS). The mortality risk was similar in the group undergoing locoregional radiotherapy alone and the group undergoing systemic chemotherapy alone [multi-adjusted hazard ratio (HR) = 0.9, P = 0.529]; this risk was 60% lower than that of the group undergoing supportive treatment (HR = 0.4, P = 0.004) and 130% higher than that of the group undergoing both systemic chemotherapy and locoregional radiotherapy (HR = 2.3, P < 0.001). In conclusion, locoregional radiotherapy, particularly when combined with systemic chemotherapy, is associated with improved survival of patients with metastatic NPC.

Long-Term Treatment After Preoperative High-Dose Chemotherapy in a Lactating Breast Cancer Patient

Breast cancer during lactation is very rare, accounting for <3% of all breast cancers. Its diagnosis and treatment is often delayed during pregnancy. We report a case of female lactating breast carcinoma in a 29-year old patient. The disease was stage IIIB (T4N1M0). The patient received preoperative induction chemotherapy and high-dose chemotherapy with peripheral blood stem cell support, followed by adjuvant chemotherapy and endocrine therapy. The metastases were detected 17 months after operation, palliative treatment including different chemotherapy for 60 cycles, locoregional radiotherapy and endocrine therapy. The total number of cycles of chemotherapy was 67, and the survival time was 118 months. We discuss the diagnosis and treatment options for breast cancer during lactation, based on a literature review.

Genetic mutations in the treatment of anaplastic thyroid cancer: a systematic review

BackgroundAnaplastic thyroid cancer (ATC) is a rare, lethal disease associated with a median survival of 6 months despite the best multidisciplinary care. Surgical resection is not curative in ATC patients, being often a palliative procedure. Multidisciplinary care may include surgery, loco-regional radiotherapy, and systemic therapy. Besides conventional chemotherapy, multi kinase-targeted inhibitors are emerging as novel therapeutic tools. The numerous molecular alteration detected in ATC are targets for these inhibitors. The aim of this review is to determine the prevalence of the major genetic alterations occurring in ATC and place the results in the context of the emerging kinase-targeted therapies.MethodsThe study is based on published PubMed studies addressing the prevalence of BRAF, RAS, PTEN, PI3KCA and TP53 mutations and RET rearrangements in ATC.Results21 articles dealing with 652 genetic analyses of the selected genes were used. The overall prevalence determined were the following: RET/PTC, 4%; BRAF, 23%; RAS, 60%; PTEN, 16%; PI3KCA, 24%; TP53, 48%. Genetic alterations are sometimes overlapping.ConclusionsMutations of BRAF, PTEN and PI3KCA genes are common in ATC, with RAS and TP53 being the most frequent. Given ATC genetic complexity, effective therapies may benefit from individualized therapeutic regimens in a multidisciplinary approach.

Cardiotoxicity of the Association Trastuzumab–Locoregional Breast Radiation Therapy: A Prospective Monocentric Study

Postoperative breast radiation therapy (RT) and trastuzumab present a significant oncologic efficacy, in terms of local control and disease-free survival. However, both treatments expose to an increased risk of cardio-vascular events. The aim of our study is to assess the cardiotoxicity of the concurrent administration of trastuzumab to adjuvant locoregional breast RT.

Brachial plexopathy due to localized axillary recurrence of breast cancer

The brachial plexopathy in breast cancer patients has been reported to be due to loco-regional metastasis or radiation plexopathy. Localized axillary recurrence (LAR) is rare. The time to LAR after primary breast cancer is various from a few months to many years. We report a patient of brachial plexopathy due to LAR that developed twenty four years after radical mastectomy and radiation therapy for breast cancer.