Outcomes following surgical treatment compared to radiation for stage I NSCLC: A SEER database analysis

Introduction

Outcomes following surgery are better than following radiation therapy (RT), for stage I NSCLC. Whether this is due to selection of healthier patients for surgery is unclear. This study was undertaken to compare outcomes between surgical patients and patients who were surgical candidates but did not receive surgery.

Methods

Data of patients with stage I NSCLC between 1988 and 2007, included in the SEER database were analyzed. Overall survival (OS) was examined by treatment type (surgery only, radiation only, surgery and radiation, and no treatment). OS was compared between RT patients who refused surgery and those not fit for surgery. Cox proportional hazards model was used to compare outcomes by treatment type.

Results

Data from 8579 patients with stage I NSCLC during 1988–2007 were analyzed. Use of RT alone increased during the study period. An increasing proportion of patients with stage I lung cancer chose to have no treatment. On multivariate analysis, OS was better among patients who had surgery. There was a 56% improvement in survival among patients who had surgery compared to fit patients who refused surgery (HR 0.437, 95% CI 0.301–0.632). Patients who refused surgery had a better OS than those who were not fit for surgery (log-rank p = 0.01). Patients who received RT alone or no treatment had a significant improvement in five-year OS during the latter part of the study period (1998–2002 vs. 1988–1992).

Conclusions

In medically fit patients, outcomes following surgery are better than those following conventional radiation. Hence surgery should be chosen over conventional radiation, whenever possible. Outcomes following RT show an improvement over time reflecting improvement in radiation techniques.     

Quality of life, survivorship, and psychosocial adjustment of young women with breast cancer after breast-conserving surgery and radiation therapy

PURPOSE/OBJECTIVES: To examine changes in quality of life (QOL), psychosocial adjustment, and survivorship issues over time of women younger than 45 years who underwent breast-conserving surgery and radiation therapy (RT) for breast cancer. DESIGN: Repeated measures, longitudinal design. METHODS: Data were collected at four time points: start of RT, midpoint of RT, end of RT, and six months after RT. Three instruments were used to collect data: Quality-of-Life Index, Psychosocial Adjustment to Illness Scale, and the newly developed Adaptation to Survivorship Experience. Subjects also participated in an indepth interview at the start of RT. SETTING: A large radiation oncology department located in an urban teaching hospital in the Northeast United States. SAMPLE: 23 women with newly diagnosed stage I or II breast cancer who were starting RT following breast-conserving surgery, with a mean age of 37.8 years (range = 25-45 years). MAIN RESEARCH VARIABLES: QOL, psychosocial adjustment, and adaptation to survivorship experience. FINDINGS: Although subjects adjusted their lives to accommodate RT, QOL declined from the start of RT to midpoint, with gradual improvement reported six months later. Social and sexual adjustment declined from start of RT to six months later. Negative perceptions of the survivorship experience and worry about cancer increased from the start of RT to six months later. CONCLUSIONS: Young women with breast cancer experience changes in QOL, psychosocial adjustment, and adaptation to survivorship issues during RT. Changes may not reflect what is observed in clinical practice. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to be aware of changes in QOL, psychosocial adjustment, and survivorship to better understand and support young women during RT.     

Risk perception of oral cancer in smokers attending primary care: a randomised controlled trial

To encourage the public to attend and accept oral cancer screening, further understanding is required of the ability of structured information to alter patient knowledge and risk perceptions. Previous work has shown the benefit of written information for those at high risk of oral cancer, especially for tobacco smokers. This study investigated three hypotheses: first that a patient information leaflet (PIL) would enhance risk perceptions, and second that the effect of the leaflet on knowledge would be confirmed as in previous studies and third that these improvements would be associated with smoking behaviour. Patients (N = 995) attending 20 general dental practices in Northern Ireland were invited to participate, 28 refused (response rate = 97%). Patients were randomised into two groups. The experimental group received a PIL and then completed a self-report questionnaire, whereas the control group followed same procedure without the PIL. Measures included a 36 item oral cancer knowledge scale and two items to assess risk perception. Usable data were available from 944 patients; mean (SD) age = 42 (15), 65% female. Risk perceptions of oral cancer were minimally effected by the PIL (p = 0.023). This effect was demonstrable in smokers. Smokers were sixteen (95% CI: 8-30) times more likely to believe that they were at greater risk of oral cancer than non-smokers. A clear benefit of the PIL on patients' oral cancer knowledge was found, particularly for smokers and those with a history of smoking. These findings demonstrate that public awareness of smokers can be raised with written information although health beliefs such as risk perceptions require more intensive intervention.     

Larynx preservation using induction chemotherapy plus radiation therapy as an alternative to laryngectomy in advanced head and neck cancer. A long-term follow-up report.

Since 1977, we have used induction chemotherapy (CT) plus radiation therapy (RT) with curative intent in 35 advanced head and neck cancer (Ca) patients who otherwise would have required total laryngectomy. Fourteen patients had advanced Ca of the larynx or supraglottic larynx (SGL); 21 patients had Ca of the hypopharynx. In six patients the Ca was Stage III; in 26 patients it was Stage IV. Three patients had Stage II disease--2 with cancer of the pyriform sinus and one patient with Stage II SGL Ca who refused surgery. Chemotherapy consisted of platinum (P) + bleomycin in 18 patients until 1982, then P + fluorouracil in the next 17 patients. Total response rate was 77%--complete (CR) in 26% and partial (PR) in 51%. There were two toxic deaths. Surgery was limited to tracheostomy in 4 patients prior to CT and to radical neck dissection after CT in 4 others. Two patients required salvage laryngectomy at 11 and 31 months, respectively. One patient underwent partial laryngectomy with voice preservation. Thirty-two patients were evaluable for overall response after RT. Final disease-free status was achieved in 20/34. One long-term survivor was lost to follow-up (44 months) and 8 patients remained alive at 13+ to 109+ months. Median failure-free survival for all patients was no less than 24 months. Not counting 4 early deaths free of disease, 2-year local control using only chemotherapy plus radiation was 52% (16:31). Overall, 33 of 35 patients retained their voices. Sixteen patients (46%) have survived 2 years or longer. Survival of patients who achieved CR after induction chemotherapy was 48 months versus 14 months for those with less than a CR (p = 0.001). Patients with a hypopharyngeal primary had only a 33% 2-year local control rate with chemotherapy and radiation and a median survival of only 12 months versus 77% control and a minimum 39-month survival for those whose tumor arose in the larynx (p = 0.009). Induction chemotherapy plus radiation therapy is an effective strategy which can produce a high rate of larynx preservation, local control, and long-term survival in patients with advanced cancer of the larynx. Patients with hypopharyngeal primaries have a lesser rate of long-term survival and local control, despite similar overall response rates.     

Treatment of early stage breast cancer by limited surgery and radical irradiation

Eighty-five female patients with early stage breast cancer, i.e., Stage I and II were treated by limited surgery followed by radical radiation therapy at Massachusetts General Hospital between January, 1956 and December, 1974. Patients included those who were medically inoperable or who refused mastectomy. The 5-year survival rate was 83% and 76% for Stage I and II, respectively. The corresponding disease free survival (absolute) was 67% and 42%. Although the number of patients so treated is small, there was no significant difference in survival from the results of the radical mastectomy series at the same institution. No major complications were encountered. Seventeen of eighty-five patients developed minor problems; mostly fibrosis and minimal arm lymphedema stemming from older orthovoltage equipment and treatment techniques. With the current availability of megavoltage equipment, improvements in techniques and dosimetry, complications should decrease. Combined limited surgery and radical radiation therapy should be considered in those patients where a radical mastectomy is not feasible because of psychological or medical problems. Since this procedure results in a cosmetically acceptable breast, radical radiation in early stage breast cancer seems a reasonable alternative to radical mastectomy.     

Treatment results and acute and late toxicity of radiation therapy for testicular seminoma

From 1977 to 1988, 215 patients with a diagnosis of testicular seminoma were referred to the University Hospital, Hamburg, West Germany, for radiation therapy (RT). In 15 patients a careful review of the histologic condition showed signs of embryonal cell carcinoma. Three patients refused completion of therapy. No patient was lost to follow-up. On this basis, a retrospective review of 197 patients was carried out. One hundred thirty-three patients were classified as Stage I (67%), 39 as Stage II (20%), 8 as Stage III (4%), and 17 as Stage IV (9%). One hundred eighty patients had classic seminoma and 17 had anaplastic seminoma. All patients underwent high inguinal orchiectomy before treatment. Seven patients with Stages III and IV received chemotherapy before RT. Patients with Stages I and II were treated with 40-Gy photons to paraaortic and parailiac fields. Ten patients with Stage III and IV seminoma received 30-Gy photons to mediastinal and supraclavicular fields as well. Sixty patients received additional inguinal RT. The overall 5-year survival rate (corrected for intercurrent death, except for treatment toxicity) was 100% for Stage I, 100% for Stage II, 87% for Stage III, and 87% for Stage IV. The mean follow-up time was 6.3 years (range, 0.6 to 11.9 years). An evaluation of all patients showed no difference according to histologic condition or prior chemotherapy. Mediastinal and supraclavicular irradiation showed no improvement in treatment results. Acute toxicity consisted of mild to moderate emesis, increased bowel frequency, erythema, and, in four cases leucopenia and thrombopenia (all World Health Organization [WHO] Grades I to II). However, one patient died of a pulmonary fibrosis 1 month after mediastinal irradiation and 2 months after polychemotherapy, and a gastroduodenal ulcer developed in another patient 1.5 months after paraaortic RT and prior polychemotherapy. Overall, the data suggest that to avoid overtreatment and consecutive treatment morbidity reduced doses of 30 Gy and a restrictive treatment planning adapted to the individual risk are sufficient for RT for testicular seminoma. An alternative to postoperative RT in Stage I (and possibly Stage II) seminoma could be no RT, but close follow-up instead.     

Dose escalation of radical radiation therapy in non‐small‐cell lung cancer using positron emission tomography/computed tomography‐defined target volumes: Are class solutions obsolete?

This study investigated the maximum theoretical radiation dose that could safely be delivered to 20 patients diagnosed with non-small-cell lung cancer. Two three-dimensional conformal radiation therapy (RT) class-solution techniques (A and B) and an individualized three-dimensional conformal RT technique (C) were compared at the standard dose of 60 Gy (part I). Dose escalation was then attempted for each technique successfully at 60 Gy, constrained by predetermined limits for lung and spinal canal (part II). Part I and part II data were reanalysed to include oesophageal dose constraints (part III). In part I, 60 Gy was successfully planned using techniques A, B and C in 19 (95%), 18 (90%) and 20 (100%) patients, respectively. The mean escalated dose attainable for part II using techniques A, B and C were 76.4, 74 and 97.8 Gy, respectively (P < 0.0005). One (5%) patient was successfully planned for 120 Gy using techniques A and B, whereas four (20%) were successfully planned using technique C. Following the inclusion of additional constraints applied to the oesophagus in part III, the amount of escalated dose remained the same for all patients who were successfully planned at 60 Gy apart from two patients when technique C was applied. In conclusion, individualized three-dimensional conformal RT facilitated greater dose conformation and higher escalation of dose in most patients. With modern planning tools, simple class solutions are obsolete for conventional dose radical RT in non-small-cell lung cancer. Highly individualized conformal planning is essential for dose escalation.     

Concurrent pemetrexed and radiation therapy in the treatment of patients with inoperable stage III non-small cell lung cancer: A systematic review of completed and ongoing studies

Current standard for locally advanced non-small cell lung cancer (NSCLC) is combined concurrent therapy with a platinum-based regimen. Preclinical synergistic activity of pemetrexed with radiation therapy (RT) and favorable toxicity profile has led to clinical trials evaluating pemetrexed in chemoradiation regimens. This literature search of concurrent pemetrexed and RT treatment of patients with stage III NSCLC included MEDLINE database, meeting abstracts, and the clinical trial registry database. Nineteen unique studies were represented across all databases including 11 phase I studies and eight phase II studies. Of the six phase II trials with mature data available, median overall survival ranged from 18.7 to 34 months. Esophagitis and pneumonitis occurred in 0–16% and 0–23% of patients, respectively. Of the ongoing trials, there is one phase III and four phase II trials with pemetrexed in locally advanced NSCLC. Pemetrexed can be administered safely at full systemic doses with either cisplatin or carboplatin concomitantly with radical doses of thoracic radiation therapy. While results from the ongoing phase III PROCLAIM trial are needed to address definitively the efficacy of pemetrexed–cisplatin plus RT in stage III NSCLC, available results from phase II trials suggest that this regimen has promising activity with an acceptable toxicity profile.     

Radiation Therapy for Small Cell Lung Cancer: An ASTRO Clinical Practice Guideline

PurposeSeveral sentinel phase III randomized trials have recently been published challenging traditional radiation therapy (RT) practices for small cell lung cancer (SCLC). This American Society for Radiation Oncology guideline reviews the evidence for thoracic RT and prophylactic cranial irradiation (PCI) for both limited-stage (LS) and extensive-stage (ES) SCLC.MethodsThe American Society for Radiation Oncology convened a task force to address 4 key questions focused on indications, dose fractionation, techniques and timing of thoracic RT for LS-SCLC, the role of stereotactic body radiation therapy (SBRT) compared with conventional RT in stage I or II node negative SCLC, PCI for LS-SCLC and ES-SCLC, and thoracic consolidation for ES-SCLC. Recommendations were based on a systematic literature review and created using a consensus-building methodology and system for grading evidence quality and recommendation strength.ResultsThe task force strongly recommends definitive thoracic RT administered once or twice daily early in the course of treatment for LS-SCLC. Adjuvant RT is conditionally recommended in surgically resected patients with positive margins or nodal metastases. Involved field RT delivered using conformal advanced treatment modalities to postchemotherapy volumes is also strongly recommended. For patients with stage I or II node negative disease, SBRT or conventional fractionation is strongly recommended, and chemotherapy should be delivered before or after SBRT. In LS-SCLC, PCI is strongly recommended for stage II or III patients who responded to chemoradiation, conditionally not recommended for stage I patients, and should be a shared decision for patients at higher risk of neurocognitive toxicities. In ES-SCLC, radiation oncologist consultation for consideration of PCI versus magnetic resonance surveillance is strongly recommended. Lastly, the use of thoracic RT is strongly recommended in select patients with ES-SCLC after chemotherapy treatment, including a conditional recommendation in those responding to chemotherapy and immunotherapy.ConclusionsRT plays a vital role in both LS-SCLC and ES-SCLC. These guidelines inform best clinical practices for local therapy in SCLC.     

To boost or not to boost: decreasing radiation therapy in conservative breast cancer treatment when "inked" tumor resection margins are pathologically free of cancer

A retrospective study was performed to compare local treatment approaches for 108 treated breasts in 105 patients with Stage I or II breast cancer. Six cases with intraductal carcinoma have shown no evidence of recurrence. The other 102 cases had invasive cancer. In 54 treated breasts in 53 patients, the treatment approach involved surgical resection of the primary tumor, pathological determination of tumor-free "inked" specimen margins and 5000 cGy to the whole breast. Local radiation therapy (RT) boosts to the primary site were not given. This approach produced a 100% local control rate (mean follow-up of 38 months). In 28 treated breasts in 27 patients, the treatment approach involved tumor excision without evaluation of specimen margins followed by RT which included a local boost by either interstitial Iridium-192 implant or electron beam. This approach yielded an actuarial local control rate of 87% at 48 months (mean follow-up of 47 months). The difference in local control rate between the two groups was statistically significant (p less than 0.03). Among patients with clear surgical margins who received a local RT boost, 1 of 9 developed a local recurrence. Among those with tumor involving specimen margins who received a local boost, 1 of 8 developed local recurrence. Local recurrence developed more frequently among patients with poorly differentiated cancers (2 of 11 cases) than among those with other invasive cancers (3 of 91 cases). Comparison of treatment approaches was limited since poorly differentiated cancer was present in 25% of cases with unknown specimen margins, as compared with only 2% of those with clear surgical margins who did not receive a local RT boost. Our preliminary findings suggest that when "inked" primary tumor resection margins are pathologically free of cancer, 5000 cGy whole breast RT appears to be highly effective for local tumor control in patients with Stage I or II disease. Our results are inconclusive as to whether patients with poorly differentiated cancers should receive a local RT boost even when surgical margins are clear.     

Living can be hazardous to your health: how the news media cover cancer risks

For more than two decades, the news media has bombarded the public with often conflicting information about health risks, contributing to an atmosphere of hype and hysteria about cancer and other diseases. Improvements in media reporting of health risks require greater efforts by both those who cover the news and those who create it. Guidelines for bringing more perspective and balance to media coverage of risk are provided. These include putting cancer in context with other diseases, explaining absolute and relative risks, differentiating between individual and population risks, stressing the degree of uncertainty of new research and how it fits with previous data, covering the process as well as end results of science, understanding different media constraints and needs, and taking into account the diverse backgrounds and needs of the target audience-the general public.     

Surgeon perspectives about local therapy for breast carcinoma

BACKGROUND: Geographic variations in the use of mastectomy and the use of radiation therapy (RT) after breast-conserving surgery (BCS) have motivated concerns that surgeons are not uniformly adhering to treatment standards. METHODS: The authors surveyed attending surgeons of a population-based sample of patients with breast carcinoma diagnosed in Detroit and Los Angeles from December 2001 to January 2003 (n = 365; response rate, 80.0%). Clinical scenarios were used to evaluate opinions about local therapy. RESULTS: On average, surgeons reported that they devoted 31.3% of their total practice to breast carcinoma. Approximately one-half of surgeons practiced in a community hospital setting, whereas 18.8% practiced in a cancer center. Compared to low volume surgeons, high volume surgeons were more likely to favor BCS with RT for invasive breast carcinoma (60.8%, 74.0%, and 87.2% for low, moderate, and high volume surgeons, respectively, P < 0.001). Surgeons who favored BCS were more likely to perceive greater quality of life (QOL) benefits for BCS than mastectomy (85.9%) compared with surgeons who favored mastectomy (28.6%) and those who did not favor 1 procedure over the other (60.0%, P < 0.001). In a ductal carcinoma in situ scenario, 35.0% of surgeons favored BCS without RT and 61.0% favored BCS with RT. Opinions regarding the role of RT after BCS varied by geographic site, surgeon volume, and patient age. CONCLUSIONS: Variation in surgeon opinion concerning local therapy reflected clinical uncertainty about the benefits of alternative treatments. High volume surgeons more frequently endorsed current clinical guidelines that favor BCS compared with mastectomy. This may partly be explained by the greater belief that BCS confers a better patient QOL than mastectomy.     

Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer

Forty patients with advanced, resectable squamous cell carcinoma of the larynx, oropharynx, or hypopharynx whose surgery would have required total laryngectomy (TL), were treated with one to three cycles of cisplatin-based chemotherapy before local therapy with the goal of larynx preservation. Clinical complete responses (CRs) or partial responses (PRs) to chemotherapy were seen in 26 of 40 patients (65%). Three patients with primary-site disease unresponsive to chemotherapy underwent resection of the primary lesion and neck dissection followed by radiation therapy (RT). Thirty-seven patients were referred after chemotherapy for RT +/- neck dissection. Thirty-one of 40 patient (78%) were rendered disease-free (no evidence of disease [NED]). With a median follow-up of 49 months (range, 31 to 76), the overall actuarial survival rate for the group was 58% at 2 years and 33% at 5 years. The failure-free survival rate was 42% and 33% at 2 and 5 years, respectively. Seven patients refused recommended TL throughout their course. This may have adversely affected survival results. A greater proportion of patients who achieved a CR or PR to chemotherapy remained disease-free compared with those who achieved less than a PR (P less than .001). Sixteen patients relapsed, 10 with locoregional disease. Six patients underwent TL, either for initial induction failure or at relapse, for an actual larynx-preservation rate of 34 of 40 patients (85%). If the seven patients who refused TL are included, the anticipated preservation rate is 27 of 40 patients (68%). Larynx preservation with combined chemotherapy and radiation is feasible and effective in patients with advanced, resectable squamous cell carcinoma of the head and neck (SCHN). This treatment approach requires a motivated patient, careful patient monitoring, and close interdisciplinary cooperation among oncologists.     

Assessing the risk of inadvertent radiation exposure of pregnant patients during radiation therapy planning and treatment in British Columbia

PurposeTo explore health care professionals' perceptions of, and experience with, the risk of inadvertent radiation exposure to pregnant patients in radiation therapy (RT) departments.Methods and MaterialsThe survey was distributed to 342 health care professionals working in RT departments in British Columbia (BC), including radiation therapists, medical physicists, radiation oncologists, and radiation oncology residents.ResultsThere were 119 responses, 65% of who were radiation therapists. Respondents' mean duration of experience was 13.9 years (range, 1-25), over which time the BC Cancer Agency has delivered at least one course of RT to an estimated 16,000 women under the age of 50. Of the responses, 11.6% indicated that they had ever, in their training or career, encountered a situation where RT was inadvertently given to a pregnant patient. Upon reviewing anonymous comments, at least 7 discrete incidents were described. Fifty-two percent of radiation oncologists never, or only occasionally, remembered to discuss the risk of RT in pregnancy; 53% did not believe there were signs posted in their cancer center warning patients or reminding staff of this risk. Furthermore, 61% did not know if there was any patient education material designed for this purpose. Establishment of a checklist to screen for potentially fertile females prior to RT was felt to be a useful intervention by 49% of respondents.ConclusionsThere is a risk of RT exposure to pregnant patients. Procedures and policies to prevent inadvertent irradiation of pregnant patients appear to be inadequate in BC. Provincial policies should be introduced to help reduce the risk of inadvertent RT of pregnant patients.     

Targeting general practitioners: Prospective outcomes of a national education program in radiation oncology

Introduction

We report on learning outcomes of a standardized national education program aimed at improving general practitioner (GP) knowledge about radiation therapy (RT) and referral pathways to radiation oncologists (ROs).

Methods

In 2014, a GP education program was developed through the Targeting Cancer public awareness campaign of the Royal Australian and New Zealand College of Radiologists (RANZCR) Faculty of Radiation Oncology. The sessions were held in RT departments and comprised of RO‐led case‐based group learning and a department tour. Pre‐ and immediate post‐session surveys assessed four domains: Objective knowledge about RT, understanding of referral pathways to ROs, self‐reported referral behaviours, feedback on the session. A 6‐month follow up survey assessed ongoing knowledge retention.

Results

Eighteen sessions were held nationwide between October 2014 and March 2016. One hundred and seventy‐four were surveyed. Pre‐session, 96% of GPs reported their knowledge of RT required improvement. Post‐session, 95% rated their knowledge as ‘excellent’, ‘above average’ or ‘competent’. 32.5% of GPs were not aware of the location of their local RT department. 81% reported patients would benefit from having clearer referral pathways to ROs. 96% agreed the GP's role is to refer cancer patients to relevant specialists to discuss treatment options. However, only 49% were comfortable referring directly to an RO. Post‐session rose to 92%. All respondents felt the session improved their understanding of RT. In the follow up survey, 17 respondents (94%) reported the session had improved their ability to care for cancer patients.

Conclusion

A national GP education program improves GP knowledge about RT and may influence patient referrals for RT.     

Treatment of breast cancer among elderly women with segmental mastectomy or segmental mastectomy plus postoperative radiotherapy

Elderly women with cancer are often treated non-aggressively. Between January 1972 and March 1984, 128 women greater than 60 years were treated for Stage I or II breast cancer with segmental mastectomy (SGM) plus/minus postoperative radiation at one of our four area hospitals. Whereas 82% of similar patients less than 60 years were referred for postop radiation, only 39.8% of patients greater than 60 were so referred. Referral rates progressively diminished with increasing patient age above 60. Thus, we reviewed the outcome of 77 elderly women treated with SGM and 51 treated with SGM+RT. Treatment groups were similar with regard to prognostic clinical and histologic parameters. Mean follow-up is 51.4 months. Among SGM patients, 45.5% of patients between 60-70 years, 37.9% of those greater than 70, and 20% of those greater than 80 years experienced loco/regional failure prior to death. Conversely, only two local failures occurred among all elderly women treated with SGM+RT. Distant failure was approximately 11% and was unaffected by treatment. Complications of SGM+RT were modest. These data suggest that SGM+RT can be safely and effectively applied to the elderly. Moreover, the data suggests that postop radiation may be more beneficial when extended to elderly patients post segmental mastectomy than among younger women. Referring surgeons should focus upon their patients' physiologic and not chronologic age as a basis for treatment allocation decisions.     

Clinical radiosensitivity in breast cancer patients carrying pathogenic ATM gene mutations: no observation of increased radiation-induced acute or late effects.

BACKGROUND AND PURPOSE: Reports on increased late subcutaneous toxicity after radiation therapy (RT) in breast cancer patients carrying ATM gene mutations has raised concerns about RT as part of the management in these patients. The impact of ataxia-telangiectasia (A-T) heterozygosity on clinical radiosensitivity remains a matter of debate while clinical data are scarce. PATIENTS AND METHODS: Between September 1995 and December 2002 genomic DNA samples were collected from 1100 unselected breast cancer patients receiving adjuvant radiotherapy at our department. Using mutation-specific assays, we screened for frequent ATM gene mutations. Analysis of acute and late radiation-related toxicity for skin and subcutaneous normal tissue was performed in patients identified as A-T heterozygotes applying common toxicity criteria (CTC) and LENT/SOMA (late effects on normal tissue/subjective objective management analytic) scoring criteria, respectively. RESULTS: Eleven patients were identified to be heterozygous for a pathogenic ATM gene mutation. Ten patients had received at least one course of RT. Median follow-up after completion of radiotherapy was 5.1 years (range 1.7-7.2). There was no evidence of increased radiation-induced acute or late skin or subcutaneous reactions in patients treated with linac-based RT. One patient failed distantly and was subsequently irradiated at four different sites for bone and brain metastases. Local relapse occurred in the single patient who had declined adjuvant RT following breast conservative therapy. CONCLUSIONS: Our results do not provide evidence for a relative contraindication to adjuvant RT in A-T heterozygous breast cancer patients. Due to their increased cellular radiosensitivity, these patients may differentially benefit from RT and qualify for dose and volume reduction trials.     

Histotype predicts the curative potential of radiotherapy: the example of ovarian cancers

BackgroundTo explore the influence of ovarian cancer histotype on the effectiveness of adjuvant radiotherapy (RT).MethodsA review of a population-based experience included all referred women with no reported macroscopic residuum following primary surgery who underwent adjuvant platin-based chemotherapy (CT), with or without sequential RT, and for whom it was possible to assign histotype according to the contemporary criteria.ResultsSeven hundred and three subjects were eligible, of these 351 received RT. For those with apparent stage I and II tumors, the cohort with clear cell (C), endometrioid (E), and mucinous (M) disease who additionally received RT exhibited a 40% reduction in disease-specific mortality and a 43% reduction in overall mortality.ConclusionsThe curability of those with stage I and II C-, E-, and M-type ovarian carcinomas was enhanced by RT-containing adjuvant therapy. This benefit did not extend to those with stage III or serous tumors. These findings necessitate reassessments of the role of RT and of the nonselective surgical and CT approaches that have characterized ovarian cancer care.     

Palliative care at the end of life for intractable neurological diseases

Palliative care at the end of life for intractable neurological diseases has come into discussion recently. According to the care guidelines for amyotrophic lateral sclerosis (ALS), suggested by the Japan Neurology Societies, neurological doctors should primarily aim at reducing patients' pain, share decisions with patients, and care for breathing difficulties, pain, and anxieties positively with the use of narcotics, like the care for cancer patients. Between June 2003 and June 2006, 58 of 79 patients (73%) refused a treatment to prolong their life, such as tracheal positive pressure ventilation (TPPV), and 19 of 24 (79%) patients desired to remain at home; these patients represented the majority. I will introduce the examples of ALS patients who refused TPPV, those who had intubation and ventilator attachment unwillingly at the time of emergency medical admission, and those who refused tube feedings. I will also report the practice on a patient with multi-system atrophy who was not self-decisive, the procedure of easing pain and its efficacy on the 9 ALS examples of home death, and the problems seen from 10 examples of death at a hospital. Hereafter, it is necessary to discuss intensely the problems of end-of-life palliative care especially for intractable neurological diseases in order to establish a methodology and to popularize it.     

Neoadjuvant, surgery and adjuvant chemotherapy without radiation for esophageal cancer

BACKGROUND: A phase II trial to evaluate neoadjuvant (NAD), surgery and adjuvant (AD) combination chemotherapy without radiation therapy (RT) for patients with esophageal adenocarcinoma staged with endoscopic ultrasound and CT as T3N1 was carried out. METHODS: Thirty-three eligible patients were enrolled. NAD therapy was administered in two 49-day cycles and included cisplatin, floxuridine, paclitaxel and leucovorin. Esophageal resection was performed followed by AD therapy. RESULTS: Thirty-three patients initiated NAD therapy; 10 experienced grade 3 and 4 toxicities, which included leucopenia, fatigue, nausea, diarrhea and stomatitis. Additionally, 16 patients experienced grade 1 and 2 hematologic and non-hematologic toxicities. Fifteen patients were down-staged, of whom five were T2, seven were T1, and three had nodal disease with no evidence of residual cancer in the esophageal bed. Fifteen patients remained T3, and two showed progressive disease. Thirty-two patients proceeded to surgery and 30 were resected. Although all resected patients were eligible for AD therapy, 15 did not receive it either because of patient refusal or surgeon recommendation. Fifteen patients received AD therapy: nine who had remained T3 and six who had down-staged. Three patients experienced grade 3 and 4 toxicities similar to those in NAD therapy. Six patients had grade 1 and 2 toxicities. Kaplan-Meier estimates of overall survival at 1, 3 and 5 years were 73% (95% CI: 58-88%), 52% (95% CI: 34-69%) and 29% (95% CI: 13-45%), respectively. Median survival was 42 months. CONCLUSION: Deletion of RT may safely allow for more aggressive chemotherapy and increase chances of survival. The results need to be confirmed in a randomized phase II or larger phase III trial.