Krystyna Kiel

Combined simultaneous cisplatin/fluorouracil chemotherapy and split course radiation in head and neck cancer.

Fifty-three patients with stage III (eight patients, 15%), stage IV (36 patients, 68%), or recurrent disease (nine patients, 17%) entered a study of simultaneous cisplatin, 60 mg/m2 day 1, fluorouracil (5-FU) infusion, 800 mg/m2 days 1 to 5, and radiation, 2 Gy days 1 to 5, every other week for a total of seven cycles (70 Gy in 13 weeks). Patient acceptance was high, with only two patients (4%) refusing to complete therapy. The median actual dose delivered was 88% of the planned dose for cisplatin, 78% for 5-FU, and 70 Gy for radiation. Weight loss of 10% or more and severe mucositis were the most common side effects (53% and 48% incidence, respectively). All patients were followed at least 1 year (median, 51 months). While the complete response rate (55%) seemed no better than that reported in other series, freedom of progression of regional disease (73%), and the survival of all patients (median, 37 months) were substantially improved. Only 33% of partial responders have failed regionally, while 15% of complete responders have failed regionally (P greater than .10), which indicates that clinical assessment of response was unreliable. Stage, the presence of N3 disease, and delivery of less than the median actual dose received of 5-FU (but not cisplatin) were significantly associated with failure. This regimen is feasible and tolerable in this difficult patient population. It generally requires no special forced feeding techniques. Survival results from this limited institution study appear better than those using sequential multimodality therapies. With such favorable regional control, this approach may offer an alternative in the future to radical surgery and radiation in resectable disease. More definitive evaluation seems warranted.

Surgical Resection of the Primary Tumor, Chest Wall Control, and Survival in Women With Metastatic Breast Cancer

Among women presenting with de novo stage IV breast cancer, 35% to 60% undergo local therapy, presumably to avoid uncontrolled chest wall disease. Several studies suggest that resection of the primary tumor may prolong survival, but chest wall outcome data are notably lacking. The authors reviewed chest wall status, time to first progression (TTFP), and overall survival (OS) in this group of women.

Radiotherapy for breast cancer in countries with limited resources: program implementation and evidence-based recommendations.

Abstract:  Radiotherapy is an essential part of the multimodality treatment of breast cancer. Applying safe and effective treatment requires appropriate facilities, staff, and equipment, as well as support systems, initiation of treatment without undue delay, geographic accessibility, and completion of radiotherapy without undue prolongation of the overall treatment time. Radiotherapy can be delivered with a cobalt‐60 unit or a linear accelerator (linac). In early stage breast cancer, radiotherapy is an integral part of breast‐conserving treatment. Standard treatment includes irradiation of the entire breast for several weeks, followed by a boost to the tumor bed in women age 50 years or younger or those with close surgical margins. Mastectomy is an appropriate treatment for many patients. Postmastectomy irradiation with proper techniques substantially decreases local recurrences and improves survival in patients with positive axillary lymph nodes. It is also considered for patients with negative nodes if they have multiple adverse features such as a primary tumor larger than 2 cm, unsatisfactory surgical margins, and lymphovascular invasion. Many patients present with locally advanced or inoperable breast cancer. Their initial treatment is by systemic therapy; after responding to systemic therapy, most will require a modified radical mastectomy followed by radiotherapy. For those patients in whom mastectomy is still not possible after initial systemic therapy, breast and regional irradiation is given, followed whenever possible by mastectomy. For patients with distant metastases, irradiation may provide relief of symptoms such as pain, bleeding, ulceration, and lymphedema. A single fraction of irradiation can effectively relieve pain from bone metastases. Radiotherapy is also effective in the palliation of symptoms secondary to metastases in the brain, lungs, and other sites. Radiotherapy is important in the treatment of women with breast cancer of all stages. In developing countries, it is required for almost all women with the disease and should therefore be available.

Supraclavicular Nodal Failure in Patients with One to Three Positive Axillary Lymph Nodes Treated with Breast Conserving Surgery and Breast Irradiation, without Supraclavicular Node Radiation

Abstract:  The purpose of this study was to evaluate the risk factors associated with supraclavicular nodal failure (SCF) in patients with one to three positive axillary nodes treated with breast conserving surgery and axillary dissection without supraclavicular node radiation (S/C RT) to aid in the selection of patients for S/C RT. Two hundred two breast conservation patients with one to three positive axillary nodes on axillary dissection treated with breast irradiation without S/C RT and 20 patients with S/C RT between August 1985 and May 2002 were identified and retrospectively evaluated. The Kaplan–Meier method was used to determine SCF‐free and overall survival curves. Risk factors for SCF were examined. The median follow‐up from surgery was 72 months (range: 4–195). Nine of 202 patients (4%) failed in the ipsilateral breast, 4 (2%) in the ipsilateral supraclavicular lymph nodes, 4 (2%) in the ipsilateral axillary and/or internal mammary nodes and 30 (15%) distantly. The 5‐ and 10‐year SCF‐free survival was 97.92%. The overall survival at 5, 10, and 15 years was 91.35%, 75.58%, and 67.18%, respectively. SCFs were associated with high grade or ER negative cancers, but not with number of positive nodes. Two of the four SCFs were associated with distant metastases, and two with local failures. One patient with a SCF was salvaged and is disease‐free at 134 months. The overall low incidence of SCF in patients with one to three positive nodes treated with breast radiation alone after breast conserving surgery and adequate axillary dissection suggests that additional S/C RT is unnecessary in this cohort. When it occurs, supraclavicular nodal failure is often associated with distant metastases.

Technique for breast irradiation using custom blocks conforming to the chest wall contour

A technique for the treatment of the breast and regional nodes is presented. The technique involves the use of tangential fields to treat the breast and chest wall. Customized blocks which conform to the slope of the chest wall are made for each tangent field. Simulation and treatment with this technique requires no special equipment. The setup is simple and quick. A three-field technique is also described using the custom half-beam blocks; this technique avoids the use of tangential field corner blocks, thus simplifying simulation and treatment.

International Conference on Advances in Radiation Oncology (ICARO): Outcomes of an IAEA Meeting

The IAEA held the International Conference on Advances in Radiation Oncology (ICARO) in Vienna on 27-29 April 2009. The Conference dealt with the issues and requirements posed by the transition from conventional radiotherapy to advanced modern technologies, including staffing, training, treatment planning and delivery, quality assurance (QA) and the optimal use of available resources. The current role of advanced technologies (defined as 3-dimensional and/or image guided treatment with photons or particles) in current clinical practice and future scenarios were discussed.ICARO was organized by the IAEA at the request of the Member States and co-sponsored and supported by other international organizations to assess advances in technologies in radiation oncology in the face of economic challenges that most countries confront. Participants submitted research contributions, which were reviewed by a scientific committee and presented via 46 lectures and 103 posters. There were 327 participants from 70 Member States as well as participants from industry and government. The ICARO meeting provided an independent forum for the interaction of participants from developed and developing countries on current and developing issues related to radiation oncology.

Interdisciplinary Coordination for Breast Healthcare: A Rational Approach to Detection, Diagnosis, and Treatment

Breast disease diagnosis and management is a quintessential example of a process requiring multidisciplinary coordination. European guidelines consider a coordinated team approach to be the standard of care. While the necessity of multidisciplinary coordination of breast healthcare is recognized in the US, its adoption in a practical sense has been fragmented and incomplete. Interdisciplinary communication and coordination has become the cornerstone of effective cancer care, but it is not supported financially or practically by a healthcare infrastructure that primarily focuses on the reimbursement of individual specialists for procedures and therapies rather than the process by which these therapies are optimally selected and integrated. Practical obstacles to interdisciplinary care are complicated by the heterogeneity of healthcare systems that must necessarily adapt to differences in population distribution, variability in access to care, availability of trained specialists, varied models of medical care delivery, and structure of insurance coverage. The American Society of Breast Disease (ASBD) is a multidisciplinary group that focuses on how interdisciplinary breast cancer care can be successfully delivered. Since much of quality improvement hinges on outcome measurement, metrics of quality interdisciplinary care are needed to assess how well we are doing in different healthcare venues. In November 2006, the ASBD held a colloquium entitled Ensuring Optimal Interdisciplinary Breast Care in the United States, the purpose of which was to develop a framework of quality indicators related to multidisciplinary and interdisciplinary care that can be used to assess the degree to which interdisciplinary communication and coordination is taking place.

Markov model and cost-effectiveness analysis of bevacizumab in HER2-negative metastatic breast cancer.

Purpose:Metastatic breast cancer (MBC) remains an incurable disease despite advances in treatment modalities. In 2008, the FDA approved bevacizumab with paclitaxel for the initial treatment of HER2-negative MBC. The approval was then officially revoked by the FDA in November 2011. However, both the European Medicines Agency and NCCN still endorse bevacizumab for this indication. One of the greatest challenges facing health care worldwide is reconciling incremental clinical benefits with exponentially rising costs. This study aimed to assess the cost-effectiveness of bevacizumab with paclitaxel for HER2-negative MBC. Methods:A Markov decision tree using Data 3.5 (TreeAge Software Inc.) was created for decision and cost-effectiveness analyses of using bevacizumab plus paclitaxel versus paclitaxel alone as first-line chemotherapy in HER2-negative MBC using efficacy and toxicity data from the E2100 study. The model was designed from the patient and payer perspectives and sensitivity analyses were run. Results:The marginal cost between paclitaxel alone versus bevacizumab and paclitaxel was 86k with a marginal efficacy of 0.369 quality-adjusted life-years and marginal cost effectiveness of 232,720.72 USD. The expected outcome value was 1.86 for bevacizumab and paclitaxel and 1.67 for paclitaxel alone. The combination was not cost effective and only a marginal survival advantage was observed. Conclusions:This study demonstrates that, despite a significant progression-free survival advantage, the addition of bevacizumab to paclitaxel is not cost effective for the cohort of patients with HER2-negative MBC included in our analysis. Such data could be informative to policymakers who consider the health economics and incremental cost-effectiveness of medical therapies.

Patterns of locoregional failure in stage III non-small cell lung cancer treated with definitive chemoradiation therapy

PURPOSE Chemoradiation therapy (CRT) is the core treatment of locally advanced non-small cell lung cancer (LA-NSCLC), but potential toxicities limit radiation therapy dose. These toxicities, plus the advent of increasingly conformal radiation therapy, have prioritized target definition and the use of involved-field radiation therapy (IFRT). Published data largely focus on regional rather than local failure patterns. We report our pattern-of-failure experience treating patients with LA-NSCLC with definitive CRT, focusing on both local and regional recurrences with detailed dosimetric analyses of failure location. METHODS AND MATERIALS Patients treated between December 2004-2010 were included. Imaging scans from date of failure were fused with the RT-planning CT scan, and recurrent nodes were contoured to determine if the recurrence was in a previously irradiated region, defined as involved nodal recurrence (INR) versus elective nodal recurrence (ENR). Local failures were contoured and identified as in-field, marginal, or out-of-field based on dose received. Actuarial overall survival (OS) and progression-free survival (PFS) were calculated, and the cumulative incidences of local, regional, locoregional, and distant recurrence (CILR, CIRR, CILRR, CIDR) were determined with death as a competing risk. RESULTS One hundred five patients were included with a median survival of 21.8 months. The 3-year OS and PFS were 36% and 22%, respectively. The 3 year CILRR, CILR, CIRR, CIDR were 41%, 38%, 40%, and 58%, respectively. Thirty patients failed regionally, but only 7 patients developed an ENR with no concurrent local failure or INR, and only 1 of these patients did not develop distant metastases within 1 month of recurrence. A total of 21 patients (20%) developed an ENR with or without other areas of recurrence. CONCLUSIONS Elective regional recurrences rarely occurred as the sole site of failure, despite the use of IFRT. Moreover, the pattern of local failure was entirely in-field. These data strongly support field design focusing on gross nodal and primary disease.

Hyperthermia and radiation therapy for locally advanced or recurrent breast cancer.

INTRODUCTION This study aims to report the outcome and toxicity of combined hyperthermia (HT) and radiation therapy (RT) in treatment of locally advanced or loco-regionally recurrent breast cancer. PATIENTS AND METHODS Patients treated with HT and RT from January 1991 to December 2007 were reviewed. RT doses for previously irradiated patients were > 40 Gy and for RT naïve patients > 60 Gy, at 1.8-2 Gy/day. HT was planned for 2 sessions/week, immediately after RT, for a minimum of 20 min and for > 4 sessions. Superficial or interstitial applicators were used with temperature measured by superficial or interstitial thermistors based on target thickness. HT treatment was assessed by thermal equivalent dose (TED), > 42.5 °C and > 43 °C. Endpoints included treatment response, lack of local progression (local control), and survival. RESULTS 127 patients received HT and RT to 167 sites. These included the intact breast (24.4%), chest wall/skin (67.7%), and breast/chest wall and nodes (7.9%). At a median follow-up of 13 months (mean 30 ± 38), improved overall survival was significantly associated with increasing RT dose (p < 0.0001), median TED 42.5 °C ≥ 200 min (p = 0.003), and local control (p = 0.0002). Local control at last follow-up was seen in 55.1% of patients. Complete response was significantly associated with median TED 42.5 °C ≥ 200 min (p = 0.002) and median TED 43 °C ≥ 100 min (p = 0.03). CONCLUSION HT and RT are effective for locally advanced or recurrent breast cancer in patients that have been historically difficult to treat by RT alone. Over 50% of patients achieved control of locoregional disease. Overall survival was improved with local control.