Baseline staging imaging for distant metastasis in women with stages I, II, and III breast cancer.

Background: In Ontario, there is no clearly defined standard of care for staging for distant metastasis in women with newly diagnosed and biopsy-confirmed breast cancer whose clinical presentation is suggestive of early-stage disease. This guideline addresses baseline imaging investigations for women with newly diagnosed primary breast cancer who are otherwise asymptomatic for distant metastasis. Methods: The medline and embase databases were systematically searched for evidence from January 2000 to April 2019, and the best available evidence was used to draft recommendations relevant to the use of baseline imaging investigation in women with newly diagnosed primary breast cancer who are otherwise asymptomatic. Final approval of this practice guideline was obtained from both the Staging in Early Stage Breast Cancer Advisory Committee and the Report Approval Panel of the Program in Evidence-Based Care. Recommendations: These recommendations apply to all women with newly diagnosed primary breast cancer (originating in the breast) who have no symptoms of distant metastasis Staging tests using conventional anatomic imaging [chest radiography, liver ultrasonography, chest-abdomen-pelvis computed tomography (ct)] or metabolic imaging modalities [integrated positron-emission tomography (pet)/ct, integrated pet/magnetic resonance imaging (mri), bone scintigraphy] should not be routinely ordered for women newly diagnosed with clinical stage i or stage ii breast cancer who have no symptoms of distant metastasis, regardless of biomarker status. In women newly diagnosed with stage iii breast cancer, baseline staging tests using either anatomic imaging (chest radiography, liver ultrasonography, chest-abdomen-pelvis ct) or metabolic imaging modalities (pet/ct, pet/mri, bone scintigraphy) should be considered regardless of whether the patient is symptomatic for distant metastasis and regardless of biomarker profile.

Eastern Canadian colorectal cancer consensus conference: application of new modalities of staging and treatment of gastrointestinal cancers.

The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Ottawa, Ontario, October 22-23, 2010. Health care professionals involved in the care of patients with colorectal cancer participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer, such as the use of epidermal growth factor inhibitors in metastatic colon cancer, the benefit of calcium and magnesium with oxaliplatin chemotherapy, the role of microsatellites in treatment decisions for stage II colon cancer, the staging and treatment of rectal cancer, and the management of colorectal and metastatic pancreatic cancers.

Sci-Thurs PM: Delivery-05: One year of learning from incidents.

The aim of this study is to quantify the effect of an incident learning system in radiation therapy. The system is designed to detect all occurrences of "an unwanted or unexpected change from a normal system behaviour that causes or has the potential to cause an adverse effect to persons or equipment". Our application to radiation therapy defines 5 incident types, four levels of severity and four work domains where errors discovered during routine quality assurance within each domain were not classified as incidents. During 2007, we recorded, corrected, investigated, determined root cause and learned from 657 incidents. The vast majority of these incidents were classified as potential minor clinical incidents having little or no impact on patient treatment. The value of the system lies in the application of the learning portion of the investigation. We demonstrated a dramatic reduction in the rate of more severe incidents by the implementation of several simple tools. Our results also show a reduction of incidents on accelerators treating essentially a single disease site. The only treatment unit treating with both image guidance and intensity modulation recorded the fewest incidents while the cobalt unit with the least technological assistance recorded three times the average treatment unit incidents with a higher severity. Additionally, although the rate of incidents at the point of treatment delivery was low, the impact of those incidents was substantially higher than that of incidents originating during treatment planning. This system has proven to be a powerful program management tool.

Clinical use of a commercial Monte Carlo treatment planning system for electron beams.

In 2002 we fully implemented clinically a commercial Monte Carlo based treatment planning system for electron beams. The software, developed by MDS Nordion (presently Nucletron), is based on Kawrakow's VMC++ algorithm. The Monte Carlo module is integrated with our Theraplan Plustrade mark treatment planning system. An extensive commissioning process preceded clinical implementation of this software. Using a single virtual 'machine' for each electron beam energy, we can now calculate very accurately the dose distributions and the number of MU for any arbitrary field shape and SSD. This new treatment planning capability has significantly impacted our clinical practice. Since we are more confident of the actual dose delivered to a patient, we now calculate accurate three-dimensional (3D) dose distributions for a greater variety of techniques and anatomical sites than we have in the past. We use the Monte Carlo module to calculate dose for head and neck, breast, chest wall and abdominal treatments with electron beams applied either solo or in conjunction with photons. In some cases patient treatment decisions have been changed, as compared to how such patients would have been treated in the past. In this paper, we present the planning procedure and some clinical examples.

[Radiation sensitivity testing and late neurological complications following radiosurgery for AVM: the use of SF2 from fibroblasts as a predictive factor]. / Radiosensibilité et séquelles neurologiques tardives suite à la radiochirurgie de malformation artérioveineuse : la SF2 comme nouveau facteur prédictif.

PURPOSE: To identify SF2 as a prognostic factor of late complications from radiosurgery in patients treated for AVM. PATIENTS AND METHODS: Five patients with AVM treated in three canadian institutions and who suffered clinically significant neurological sequelaes secondary to radiosurgery were identified. Their fibroblasts were cultured and their radiation sensitivity tested to determine the SF2 for each patient. RESULTS: Patients who developed a neurological complication from radionecrosis, secondary to radiosurgery had an SF2 different than the two control patients with AVM and no complications and also from a group of five cancer patients without late radiation complications (P = 0.005). CONCLUSION: Radiosurgery is an elective procedure. The identification of a subgroup of patients who are radiosensitive and at a higher risk of radiation induced complications can allow the treatment team to reduce the risk of such complications. SF2 as a new predictive factor should be incorporated in predictive models of risk from treatment of AVM by radiosurgery. This work needs to be confirmed in a larger cohort of patients.

Anal intraepithelial dysplasia and squamous carcinoma in immunosuppressed patients.

OBJECTIVE: To describe a treatment and follow-up protocol for HIV patients with anal dysplasia or warts, which are at risk of malignant change. DESIGN: An ongoing study of highly selected patients referred to a single surgeon. SETTING: The Colorectal and HIV/AIDS Clinics, University of Ottawa, General Campus. PATIENTS: Ninteen young men who presented with suspicious anal lesions and were referred to the Colorectal Clinic by the HIV/AIDS Clinic, which sees approximately 800 patients per year. OUTCOME MEASURE: Significance of dysplasia or carcinoma. RESULTS: Of the 19 patients, 14 had dysplasia, carcinoma-in-situ or invasive carcinoma. All were treated with multiple mapped cold biopsies and local or wide excision as indicated. Two patients with invasive carcinoma received radiotherapy or chemotherapy, or both. CONCLUSIONS: The incidence of dysplasia or the sequence by which dysplasia progresses to invasive carcinoma is unknown. Surveillance of HIV patients, especially those with nodules or warts, by flexible sigmoidoscopy and Papanicolaou smears every 3 to 12 months is recommended, depending on the severity of the anal lesion.

A phase III study of high-dose intensification without hematopoietic progenitor cells support for patients with high-risk primary breast carcinoma.

Patients with more than nine ipsilateral lymph node involvement or inflammatory breast cancer have a 5-year survival rate of approximately 50%. We studied the efficacy of high-dose intensification, comparing it with the standard dose chemotherapy for patients with high-risk primary breast cancer. Patients with inflammatory breast cancer or more than nine ipsilateral lymph node involvement without evidence of distant metastasis were randomized to receive either standard dose 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for nine courses (control) or six courses of FAC followed by two courses of cyclophosphamide (5.25 g/m2), etoposide (1,500 mg/m2), and cisplatin (165 mg/m2) (HDCVP). The study was terminated in 1998 because of slow accrual of patients. Forty-six patients were entered in the study. At 4 years, the overall survival was 72.8% (SE 11.9%) and 61.7% (SE 12.4%), and disease-free survival were 45.5% (SE 12.3%) and 33.7% (SE 11.9%) for the control and HDCVP groups, respectively (p = 0.757 and 0.720). With the small number of patients in our study, a small overall survival benefit of high-dose intensification compared with the standard therapy cannot be excluded. However, any substantial benefit is unlikely.

[In vitro radiosensitivity of skin fibroblasts can identify a group of patients with complications in various health tissues after radiotherapy]. / La radiosensibilité in vitro des fibroblastes de la peau peut identifier un groupe de patients ayant des complications dans différents tissus sains après radiothérapie.

PURPOSE: A retrospective study of the in vitro radiosensitivity of skin fibroblasts derived from two groups of patients treated by definitive radiotherapy for a variety of tumors who either displayed or did not display severe complications. PATIENTS AND METHODS: Seven radiotherapy patients were selected: three were treated for head and neck, prostate and non-Hodgkin lymphoma tumors, and did not develop any significant complications (control group); four patients were treated for bladder, thyroid, head and neck and anal canal tumors and developed serious acute and especially late reactions (hypersensitive group). Primary cell cultures of skin fibroblasts were established and their radiosensitivity studied by the clonogenic assay after exposing to single radiation doses ranging between 1 and 8 Gy. RESULTS: The survival fraction at 2 Gy (SF2) ranged from 0.27 to 0.38, with a mean of 0.33 for the control group, and from 0.10 to 0.20 with a mean of 0.17 for the hypersensitive group. The Mann-Whitney non-parametric test showed that the difference between the two means was statistically significant (p = 0.03). CONCLUSION: The data are in favor of a correlation between the radiosensitivity of patients' fibroblasts and the reactions of different normal tissues to radiotherapy. This association supports the use of the clonogenic survival, or a surrogate test, as a predictive assay. The multiplicity of normal tissues and organs implicated in this association suggests the existence of genetic factors that determine, at least in part, the radiosensitivity of target cells involved in the expression of normal tissues complications following radiotherapy.

[Treatment of cancer of the bladder in elderly patients with an intra-arterial chemotherapy and radiotherapy combination: 10-year experience]. / Traitement du cancer de la vessie chez les patients âgés par association de chimiothérapie intra-artérielle et de radiothérapie: 10 ans d'expérience.

PURPOSE: Analysis of the results obtained in elderly (75 years and older) included a phase II trial combining intra-arterial cisplatin and concurrent radiation into invasive bladder cancer. PATIENTS AND METHODS: Thirty-five patients (28 males and 7 females) were accrued from 1985 to 1996. There were 1 Ta, 4 T2, 11 T3A, 12 T3B, 3 T4A, and 4 T4B patients. Nine had unilateral hydronephrosis and two bilateral hydronephrosis. There were 28 transurethral resections which were incomplete in 23 patients. Intra-arterial cisplatin was given as 2-4 hours infusion (60-90 mg/m2) split through both internal iliac arteries on day 1, 14, 21, and 42. Irradiation to the pelvis was started on day 14 and consisted of 40 Gy/20 fractions followed by a boost of 20 Gy/10 fractions to the tumor with margins of 2 cm. RESULTS: Thirty (86%) completed fully the protocol. One patient died from sepsis secondary to the treatment. The tumor response was evaluable in 29 patients and complete response was observed for 27 of them. Five of these 27 patients had an isolated bladder relapse which was salvaged by cystectomy in two patients. There were 11 deaths from bladder cancer (31% of the patients): 9 from distant metastase, one from local failure, and one from treatment. CONCLUSION: This combined modality yields excellent results with high complete response rate and good tolerance. This approach may therefore be particularly appropriate for the elderly.

Bone marrow metastasis in astrocytic gliomata.

With the increasing survival time of many pediatric patients with malignancies, unexpected symptoms or signs require diligent search for rare complications or second cancers related to the disease or treatment. We recently encountered a patient with extensive glioblastoma multiforme who developed pancytopenia six months after completion of treatment with craniospinal radiation and chemotherapy with etoposide and cyclophosphamide. Bone marrow aspirate and biopsy confirmed bone marrow metastasis from the brain tumor. He showed good partial remission with chemotherapy with carmustine and cis-platinum as demonstrated by serial bone marrow aspirate for cytology and cytogenetics and enjoyed good quality of life for eight months. 14 other patients with astrocytic glioma, two of whom are children, are reported in the literature to have diffuse bone marrow metastasis. Therefore, in patients with malignant astrocytic tumor, bone marrow metastasis, though not common, should be considered when bone pain or cytopenias occur, especially when prolonged.

[Late effects of ionizing radiations on head and neck region tissues]. / Effets tardifs des radiations ionisantes sur les tissus de la sphère otorhinolaryngologique.

Numerous structures are included in the irradiated volume of patients presenting with head and neck cancer: skin, mucosa, bone, teeth, cartilage, muscles, salivary glands, etc. Curative intent treatment of such tumours requires aggressive approach which can lead to severe sequellae. These sequellae are in most cases dose-dependent and volume-dependent. However, an appropriate technique might decrease the severity of such sequellae. Details of these late changes are presented, including their pathophysiology, clinical syndromes, potential treatment, and prevention.

The role of palliative thoracic radiotherapy in non-small cell lung cancer.

Non-small cell lung cancer is the most common cause of cancer death in both males and females. Despite this high incidence and mortality, comparatively little research has addressed the palliative treatment of thoracic symptoms. Until recently, information regarding the indications and effectiveness of radiation in this setting was obtained from retrospective reviews of single institutional experiences. More recently, three major randomized trials from the UK Medical Research Council (1991, 1992, 1994) have addressed the use of external beam radiation in randomized comparisons of different dose and fractionation strategies for patients with non-small cell lung cancer and symptoms due to intra-thoracic tumor. These studies show that shorter fractionation schemes provide equivalent palliation and essentially equivalent survival in the patient groups studied. Moreover, they provide estimates of the probability of successful palliation of common symptoms, and estimates of the toxicity of each regimen. A panel of oncologists with expertise in radiation oncology, medical oncology and epidemiology discussed the above trial results and a literature review. The panel concluded that radiation was indicated in the palliation of hemoptysis, chest pain, dysphagia, and dyspnea, and that the results of the MRC studies provided reasonable estimations of the efficacy and toxicity of radiation in this setting. These studies show that symptoms are more often than not improved with palliative radiotherapy (symptom improvement rates ranged from about 50 to 85%) and that palliation lasted for a substantial portion of the patients' remaining survival. The panel could not reach uniform consensus on the appropriate fractionation for radiation given with palliative intent. The panel agreed that favourable patients with stage IIIB NSCLC should be offered combined modality therapy with the intent of prolonging survival, and that patient preferences regarding the risks and benefits of this therapy should be considered. Further study was recommended, namely, a randomized trial evaluating five fractions of radiation vs a single fraction, using patient-based evaluation of palliation. The panel also recommended phase II development of a combined chemotherapy and low-dose radiation protocol appropriate for future study.

Childhood medulloblastoma in Ontario, 1977-1987: population-based results.

A retrospective review was carried out to study children, not more than 16 years old, with a confirmed diagnosis of medulloblastoma, who were residents of the Province of Ontario at the time of diagnosis between 1977 and 1987 inclusive. The provincial tumour registry provided the population database. One hundred and eight children with medulloblastoma were identified of whom 72 (67%) were initially treated at University of Toronto Centres and 36 (33%) at other Health Science Centres, hospitals, and Regional Cancer Centres (RCC) in Ontario. The hospital/Cancer Centre records were reviewed. The 5-year relapse-free survival (RFS) for all patients treated in Ontario was 58% (SE = 5%). Those treated in Toronto had a 5-year RFS of 65% (SE = 6%) compared to 44% (SE = 8%) for those treated in other RCCs in the province (P = 0.02). Relapse-free survival for the RCCs ranged from 25 to 60%, with a trend for improved survival with increasing centre size. Univariate analysis of determinants of relapse-free survival for all 108 patients showed the following variables to be significant: T-stage (Tx + T1 + T2 vs. T3A + T3B) P = 0.0004, M-stage (M0 + Mx vs. M1-4) P = 0.0006, extent of resection (total vs. less than total) P = 0.002, radiotherapy (craniospinal irradiation and posterior fossa boost vs. other) P = 0.02, and treatment centre (Toronto centres vs. RCC) P = 0.02. Cases treated at centres outside metropolitan Toronto had a nearly two-fold (relative risk = 1.93; 95% confidence interval = 1.07, 3.47) greater risk of recurrence or death than those seen in Toronto. However, in multivariate analysis this difference was not quite significant (P = 0.07) after controlling for stage (T and M), extent of resection, meningitis, and gender. These data suggest that patients with medulloblastoma should be referred for treatment to large centres with major pediatric neurosurgical and oncology resources.

Interstitial brachytherapy for penile carcinoma: an alternative to amputation.

From 1987 to 1994, 15 patients with penile saquamous cell carcinoma were referred to the Ottawa Regional Cancer Centre. Seven had already been managed surgically. The other eight were treated with interstitial implantation. Mean age was 58 years (range 39-80). Two patients had previous incomplete local excision and six had biopsy only, with tumor from 1.5 to 4 cm in diameter. Six tumors were located on the glans, one on the corona and one at the base. All were clinically node negative. Six patients were implanted using a rigid technique with a fixed array of steel needles in pre-drilled plexiglass templates, and two with flexible nylon tubing. Implants were manually afterloaded with Iridium-192 wire. The prescribed dose of 60-65 Gy was delivered in 2.5-5.5 days. Local tumor control is 100% at a mean follow-up of 37 months (range 6-64). One patient died of metastases at 15 months with the primary controlled. The remaining seven patients are alive without evidence of disease. Six who were sexually active, continue to be so. One patient has a urethral stricture requiring dilatations. Cosmesis is generally good: mild to moderate hypopigmentation, telangiectasia and fibrosis may develop at the implant site. Intersititial brachytherapy for T1 or minimally invasive T2 penile squamous cell cercinoma up to 4 cm in diameter provides excellent local control with preservation of function and is a viable alternative to amputation.

Asymmetric arc technique for posterior pharyngeal wall and retropharyngeal space tumors.

PURPOSE: Tumors of the posterior pharyngeal wall and nasopharyngeal cancer with retropharyngeal extension can partly encircle the cervical vertebrae. Treating the patient within spinal cord tolerance can cause a geographic miss. A simple technique has been developed to avoid this problem. METHODS AND MATERIALS: The standard fields for posterior pharyngeal wall and nasopharyngeal tumors are used up to 36-40 Gy. A planning computed tomography (CT) scan is taken during the second or third week of treatment with the patient fitted in a new shell ensuring that the cord is straight and parallel to the treatment couch. The asymmetric arc technique consists of two posterior arcs with closure of one jaw beyond the central axis. Each arc delivers the total dose to each ipsilateral side, while the median region of the U-shaped volume is treated by the summation of both arcs. RESULTS: We have treated 10 patients using asymmetric arcs in the last 3 years. This technique proved to be a versatile way of treating targets wrapped around the spine. The technique allows better individualization for target volume irregularities than the partial rotation with a central bar.

Brachytherapy of neck metastases.

Brachytherapy with iridium 192 was used in 20 patients with recurrent or persistent neck metastases from a primary head and neck carcinoma. Nine patients had intra-operative brachytherapy in combination with a neck dissection. Three patients had an implant as a boost following external beam radiotherapy. Eight patients were treated by brachytherapy alone for unresectable neck recurrence ranging from 5 to 10 cm in diameter. Nineteen patients were evaluable for neck control: 15 patients had complete clearance of tumor and 13 patients were controlled at time of death or last follow-up. There were few complications from treatment. Five patients are alive at 5, 14, 16, 22, and 27 months post-implant with two patients having developed a second primary. Seven patients died from distant metastases, four from regional disease and four from intercurrent illness. Indications are summarized for this frequently forgotten but useful last option for patients with persistent or recurrent neck metastases.

Effect of intersource spacing on local control and complications in brachytherapy of mobile tongue and floor of mouth.

From 1971 to 1988, 133 T1 and 141 T2 biopsy-proven squamous cell carcinomas of mobile tongue and floor of mouth were definitively managed by Iridium-192. Implantations were performed using either guide gutters or afterloading plastic catheters. The prescribed dose at the reference isodose (85% of the basal dose rate, Paris system) was 60-70 Gy. Total dose was not adjusted to dose rate or tumor volume. Results of the 274 implants have been analysed to look for a possible influence of intersource spacing on local control and necrosis. Follow up for patients free of local recurrence is 1-180 months with median of 35 months. The 274 tumors were divided into two groups according to intersource spacing: 9-14 mm (n = 204), and 15-20 mm (n = 70). At 5 years, the estimated local control (Kaplan Meier) was 86% and 76%; respectively (p = 0.13); the necrosis rate was 33% and 46%, respectively (p = 0.04). Multivariate analysis shows that dose and activity of wires were significantly related to local control, while only tumor site was predictive of necrosis; there was a non-statistically significant relationship between intersource spacing of wires and local control (p = 0.055). When considering only patients with oral tongue cancers, necrosis was significantly related to activity of wires (p = 0.013), and there was a non-significant trend to a relationship between necrosis and intersource spacing (p = 0.066) and tumor diameter (p = 0.065). For patients with floor of mouth cancer, none of these factors was significantly related to necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Dosimetry of intraluminal brachytherapy.

Dose specification in intraluminal brachytherapy varies considerably in the literature. A terminology is proposed, inspired from the Paris System of interstitial brachytherapy, to define some dosimetric guidelines. The dose is specified in the central plane which is a plane perpendicular to the source and passing through its centre. The reference dose rate is calculated in this plane. The treated volume is the volume encompassed by the reference isodose. The hyperdose sleeve is the volume receiving a dose equal to or greater than twice the reference dose. A study of the dose distribution along a linear source of iridium-192 was undertaken. Results obtained, also valid for caesium-137 and cobalt-60, show that the radius of the hyperdose sleeve is relatively independent of the length of the source. It is approximately 0.6 times the distance between the source axis and the point of dose specification when the active length varies from 3 to 20 cm. Reporting not only the dose, but also the thickness of tissue covered by the reference isodose and the thickness of tissue included in the hyperdose sleeve, is recommended to assist in evaluation of the results of treatment and to facilitate the exchange of clinical information in intraluminal brachytherapy. Practical examples are given.

Induction chemotherapy in head and neck cancer: results of a phase III trial.

Between December 1982 and October 1986, 131 patients with stage II-III-IV squamous cell carcinoma of the oropharynx or oral cavity were randomized to induction chemotherapy, consisting of bleomycin (10 mg/m2/day in continuous infusion from day 1 to day 5), methotrexate (120 mg/m2 on day 2) followed by folinic acid, 5-fluorouracil (5 FU) (600 mg/m2 on day 2), and cisplatin (120 mg/m2 on day 4) every 4 weeks for a total of three cycles followed by definitive locoregional treatment versus locoregional treatment alone. The modalities of definitive treatment (radiotherapy +/- surgery) were chosen prior to randomization. A total of 116 patients were evaluable. Of 55 patients in the chemotherapy arm, four (7%) had a complete response (CR) and 23 (42%) a partial response (PR) following the induction regimen. At the completion of locoregional treatment, 76% (42 of 55) of patients in the experimental group were in CR compared to 89% (54 of 61) in the control group. There was no difference in survival, cause-specific survival, and pattern of relapse between both groups. The median survival was 22 months in the chemotherapy group and 29 months in the control group. Responders to chemotherapy did not fare better than nonresponders. Chemotherapy-related toxicities were few and most of them related to cisplatin which was reduced to 100 mg/m2 for 35 patients. There were no treatment-related deaths and, in the experimental arm of the trial, no increased morbidity from locoregional treatment. This induction regimen does not offer any advantages over standard treatment.