Prognostic relevance of disseminated tumour cells in bone marrow of patients with transitional cell carcinoma

ObjectiveThis prospective study is the first immunocytochemical investigation of the frequency and prognostic value of CK+ tumour cells in the bone marrow of patients with transitional cell carcinoma (TCC).MethodsBone marrow aspirates from 228 TCC patients were taken preoperatively. Cytospins were made and stained by immunocytochemistry using the monoclonal antibodies CK2 and A45-B/B3. 27 patients with no evidence of any malignant disease served as control group.ResultsCK+ tumour cells were detected in 28% (63/228) of the TCC patients. No CK+ cells (0/27) were detected in the control group. In multivariate analysis the detection of ⩾3 CK+ cells in bone marrow was an independent prognostic factor (hazard ratio = 2.7, p < 0.05) in patients with T2–4 tumour classification.ConclusionDisseminated CK+ cells play a role in the biology of tumour spread of TCC, and their immunocytochemical detection can be useful in assessing the prognosis of TCC patients with an invasive tumour.     

Influence of zoledronic acid on disseminated tumor cells in primary breast cancer patients

BackgroundThe presence of disseminated tumor cells (DTCs) in bone marrow of patients with early breast cancer (EBC) has been correlated with increased risk of metastatic disease or locoregional relapse. Zoledronic acid (ZOL) treatment has reduced DTCs in the bone marrow of patients with EBC in several studies. This controlled study sought to confirm these observations.Patients and methodsPatients with EBC and DTC-positive bone marrow were randomized (N = 96) to treatment with ZOL plus adjuvant systemic therapy or adjuvant systemic therapy alone. The change in DTC numbers at 12 months versus baseline was measured.ResultsDTC-positive patients treated with ZOL were more likely to become DTC-negative after 12 months of treatment compared with the controls (67% versus 35%; P = 0.009). At 12 months, DTC counts decreased to a mean of 0.5 ± 0.8 DTCs in the ZOL group and to 0.9 ± 0.8 DTCs in the control group. In addition, ZOL was generally well tolerated.ConclusionsTreatment with ZOL improves elimination of DTCs. Further studies are needed to determine whether the reduction in DTCs by ZOL provides clinical benefit.     

Local therapy is critical in localised pelvic rhabdomyosarcoma: experience of the International Society of Pediatric Oncology Malignant Mesenchymal Tumor (SIOP-MMT) committee

BackgroundLocalised pelvic rhabdomyosarcomas (pRMS) are rare tumours with a poorer prognosis than the majority of RMS. This study analysed patient outcome according to the type of local therapy delivered and the effect of disease-related factors on prognosis.Patients and methods97 children with localised pRMS were enrolled in the SIOP-MMT84, 89 and 95 studies. After primary surgery or biopsy, all children received ifosfamide/actinomycin/vincristine-based chemotherapy. Radiotherapy and surgery were planned in patients failing to achieve complete remission.ResultsMedian age at diagnosis was 52 months [5 months–18 years]. IRS staging was I for five patients, II for 15 and III for 77. Patients had embryonal RMS (N = 41), alveolar RMS (N = 29), botryoid RMS (N = 3), or not otherwise specified RMS (N = 24).Outcome87 patients achieved local control (90%), 37 relapsed (43%), mainly locally (84%). With a median follow-up of more than 10 years [4–22 years], 5-year OS was 66% (95% CI: 56–75%) and EFS was 52% (95% CI: 42–61%). Among the 18 IRS-I/II patients treated without radiotherapy, 15 survived. Seven out of the 20 IRS-III patients treated without local therapy died. In multivariate analysis, IRS staging, age greater than 10 years and lymph node involvement had a negative impact on OS. Perineal/perianal locations had a trend towards a worse prognosis.ConclusionpRMS still have a relatively poor prognosis. Radiotherapy or brachytherapy is necessary for all IRS-III patients including those with radiological complete remission after neoadjuvant chemotherapy with or without surgery. Radiotherapy may be withheld in IRS-I patients and children under 3 years with IRS-II pRMS.     

Central nervous system atypical teratoid rhabdoid tumours: the Canadian Paediatric Brain Tumour Consortium experience

BackgroundAtypical teratoid rhabdoid tumours (ATRT) are aggressive brain tumours mostly occurring in early childhood. Largest published series arise from registries and institutional experiences (1–4). The aim of this report is to provide population-based data to further characterise this rare entity and to delineate prognostic factors.Patients and methodsA national retrospective study of children ⩽18 years diagnosed with a central nervous system (CNS) ATRT between 1995 and 2007 was undertaken. All cases underwent central pathology review.ResultsThere were 50 patients (31 males; median age at diagnosis of 16.7 months). Twelve patients were >36 months. Infratentorial location accounted for 52% of all cases. Nineteen patients (38%) had metastatic disease. Fifteen (30%) underwent gross total resection (GTR). Ten patients (20%) underwent palliation. Among the 40 remaining patients, 22 received conventional chemotherapy and 18 received high dose chemotherapy regimens (HDC); nine received intrathecal chemotherapy and 15 received adjuvant radiation.Thirty of the 40 treated patients relapsed/progressed at a median time of 5.5 months (0–32). The median survival time of the entire cohort was 13.5 months (1–117.5 months).Age, tumour location and metastatic status were not prognostic. Patients with GTR had a better survival (2 years overall survival (OS): 60% ± 12.6 versus 21.7% ± 8.5, p = 0.03). HDC conferred better outcome (2 years OS 47.9% ± 12.1 versus 27.3% ± 9.5, p = 0.036). Upfront radiation did not provide survival benefit. Six of the 12 survivors (50%) did not receive radiation.ConclusionThe outcome of CNS ATRT remains poor. However, the use of HDC provides encouraging results. GTR is a significant prognostic factor. The role of adjuvant radiation remains unclear.     

The prognostic value of fast molecular response of marrow disease in patients aged over 1 year with stage 4 neuroblastoma

BackgroundQuantitative real-time (q)PCR for detection of minimal residual disease (MRD) in children with neuroblastoma (NB) can evaluate molecular bone marrow (BM) response to therapy, but the prognostic value of tumour kinetics in the BM during induction treatment remains to be established. The purpose of this study was to analyse at which time points MRD detection by sequential molecular assessment of BM was prognostic for overall survival (OS).MethodsIn this single centre study, qPCR was performed with five NB-specific markers: PHOX2B, TH, DDC, GAP43 and CHRNA3, on 106 retrospectively analysed BM samples of 53 patients >1 year with stage 4 neuroblastoma. The prognostic impact of MRD at diagnosis (n = 39), at 3 months after diagnosis (n = 38) and after completing induction chemotherapy (n = 29) was assessed using univariate and bivariate Cox regression analyses.ResultsThere was no correlation between tumour load at diagnosis and outcome (p = 0.93). Molecular BM remission was observed in 11/38 (29%) of patients at 3 months after diagnosis and associated with favourable outcome (5-y-OS 62 ± 15.0% versus 19 ± 8%; p = 0.009). After completion of induction chemotherapy, BM of 41% (12/29) of the patients was still MRD positive, which was associated with poor outcome (5-y-OS 0% versus 52 ± 12%; p < 0.001). For both time points, the prognostic value of molecular response remained significant in bivariate analysis.ConclusionsMRD detection measured by a panel of NB specific-PCR targets could identify fast responders, who clear their BM early during treatment. Fast molecular response was a prognostic factor, associated with better outcome. Our data indicate that MRD analysis during induction therapy should be included in prospective MRD studies.     

Single fraction radiotherapy for small superficial carcinoma of the skin

AimsTo define the optimal dose and maximum tumour size of basal and squamous cell carcinoma of skin that can be treated by single fraction radiotherapy.Materials and methodsA review was undertaken of 1005 lesions of basal/squamous cell carcinoma of the skin involving 806 patients treated at a single centre with 10 years of follow-up. Doses of 18, 20 and 22.5 Gy were used. The recurrence and necrosis free survival rates for different anatomical sites and radiation doses were calculated.ResultsThe overall disease-free and necrosis-free rates at 5 years were 90% and 84%, respectively. The crude 10-year recurrence rate was 4% (95% CI 3.4–5.4%), with late skin necrosis at 6% (95% CI 4.8–7.2%). There was no difference in tumour recurrence rates between 20 and 22.5 Gy (P = 0.3), but there was a significantly higher skin necrosis rate at the treated site in the patients who had received 22.5 Gy (P = 0.003). Most skin necrosis healed spontaneously, with only 16% requiring surgical intervention. Tumours involving the inner canthus had a significantly higher recurrence rate than those involving other areas of the head and neck.ConclusionsSingle fraction radiotherapy is an acceptable treatment for small superficial BCC and SCC of the head and neck region in patients who have difficulty attending multiple hospital visits as long as the field size required for treatment is no larger than 3 cm in diameter. The optimal applied dose for such a lesion on a flat surface is 20 Gy.     

Primary bone lymphoma--treatment and outcome

AimsA retrospective review of patients with histologically confirmed primary bone lymphoma (PBL) diagnosed and treated at a single tertiary referral centre between 1985 and 2003.Materials and methodsThe medical records of all patients treated for histologically primary bone lymphoma were identified using the hospital data base. Data was obtained on patient demographics, stage, treatment and outcome.ResultsTwenty-two patients with PBL were identified. Seventeen had localised disease and five had multifocal bone involvement. The median age was 50 years. Of the patients who could be graded according to the International Prognostic Index (IPI), 12 cases were classified as low risk, seven as intermediate risk and one as high risk. All patients received chemotherapy; 19 with an anthracycline-containing regimen. Eighteen patients were treated with radiotherapy to a median total dose of 40 Gy (range 30–50 Gy). Three patients had surgery instead of radiotherapy as local treatment (one fibulectomy and two endoprosthetic replacements). The median follow-up was 84.5 months (range 3–206 months). The overall 10-year survival was 74%; 92% for low-risk IPI vs 73% for intermediate-risk IPI (P = 0.27). The 10-year relapse-free survival was 85% overall and 83% for both low- and intermediate-risk IPI (P = 0.87). Local relapse was seen in one patient. Orthopaedic complications occurred in two patients — one developed a pathological fracture after biopsy before radiotherapy and the other developed avascular necrosis outside the irradiated area.ConclusionsCombined modality treatment for PBL results in good local control and survival rates with acceptable toxicity.     

Hypofractionated conformal irradiation of patients with malignant glioma

PurposeThe aim of the study is to evaluate the effect of a conformal irradiation in short fractionation scheme of 49.5 Gy in 15 fractions in an overall time of 3 weeks, in terms of overall survival (OAS) and progression free survival (PFS) rates in brain glioma patients.Patients and methodsA prospective study was conducted on 54 brain glioma patients and was carried out in the Radiation Oncology Department, South Egypt Cancer Institute, Assiut University during the period from April 2006 till June 2009. Patients were treated by hypofractionated conformal irradiation (49.5 Gy/15 fractions/3 weeks).ResultsThe median follow up was 23 months (range: 9–39 months). Two-year OAS and PFS rates were 68% and 60%, respectively. In univariate analysis, age >50 years, poor performance status [Karnofasky score of ?40–?70%], poor neuroperformance status of score III, high-grade tumor [glioblastoma multiforme], and biopsy were all associated with statistically significant reduction in OAS and PFS rates. Multivariate analysis, showed that age >50 years and glioblastoma pathology were the only independent prognostic factors that were associated with poor OAS (p = 0.003 and p = 0.004, respectively), and PFS (p = 0.027 and p = 0.011, respectively).ConclusionHypofractionated conformal radiotherapy was as effective as the conventional radiotherapy, with time sparing for patients, and for radiation oncology centers. Hypofractionated radiotherapy may be considered the radiotherapy regimen of choice in clinical practice for patients with gliomas.     

External-beam radiotherapy in T1-2 N0 penile carcinoma

AimsTo review the outcome of 41 patients with invasive carcinoma of the penis treated with external-beam radiotherapy using a consistent technique and dose.Materials and methodsForty-one patients with carcinoma of the penis treated at Christie Hospital, Manchester, UK, between 1995 and 2000 were reviewed retrospectively. Radiotherapy was delivered using 4 MV linear accelerators with a dose of 50 Gy or 52.5 Gy in 16 fractions over 22 days.ResultsThe distribution of patients according to stage was T1 = 37, T2 = 4, N0 = 40, N3 = 1. Median follow-up was 4.5 years. The local control rate was 62%, nodal relapse-free rate of 88%, relapse-free rate of 51% and overall survival of 88% at 5 years. All recurrences were salvaged by surgery. Penile ulceration occurred in 8% and urethral stenosis requiring dilatation in 29%. There were no penectomies for penile necrosis.ConclusionEBXRT may be offered for T1-2 cancer of the penis with close surveillance to detect local recurrences early for salvage surgery without jeopardising overall survival. It remains an alternative option to penis-preserving surgery and should be discussed in a multidisciplinary setting and with the patient.     

Outcomes in paediatric metastatic rhabdomyosarcoma: Results of The International Society of Paediatric Oncology (SIOP) study MMT-98

PurposeResults are presented of the SIOP study MMT-98 for paediatric metastatic rhabdomyosarcoma (RMS), which evaluated intensive chemotherapy followed by low intensity ‘maintenance’ chemotherapy in standard risk patients (SRG). For poor risk patients (PRG), the value of a therapeutic window study, sequential high dose monotherapy to achieve a complete response (CR) followed by low dose maintenance chemotherapy was examined.Patients and methodsFrom November 1998 to 2005, 146 patients aged 6 months to 18 years with metastatic RMS were entered. Forty-five were SRG, i.e. age < 10 years and no bone marrow or bone involvement. Treatment was a 6-drug regimen with local therapy of surgery and/or radiotherapy followed by maintenance of 9 courses of vincristine, actinomycin D and cyclophosphamide (VAC). One hundred and one patients were PRG, i.e. >10 years, or with bone marrow or bone metastases. An upfront window study, high dose monotherapy, local treatment and then VAC maintenance therapy were given.ResultsWith a median follow-up of 1.52 years, the 3-year event-free survival (EFS) and overall survival (OS) for SRG were 54.92% and 62.14%, respectively, whilst for the PRG 16.17% and 23.17%. The corresponding adverse hazard ratio (HR) for the PRG was HR = 2.65 (95% CI 1.63–4.31, p-value < 0.001) for EFS and HR = 2.51 (CI 1.53–4.11, p-value < 0.001) for OS.ConclusionSRG patients’ EFS and OS were comparable to those of previous studies. For PRG patients there was no improvement in survival.     

Does Magnetic Resonance Imaging of the Spine Have a Role in the Staging of Prostate Cancer?

AimsMagnetic resonance imaging (MRI) is an effective method for evaluating the spine in patients with a high risk of metastatic disease. The aim of this study was to compare MRI spine with radionuclide bone scan in detecting spinal metastases for staging prostate cancer patients.Materials and methodsA cohort of 99 patients with locally advanced prostate cancer at high risk of skeletal metastasis (prostate-specific antigen > 10 ng/ml, composite Gleason score ≥ 8) or equivocal findings on bone scan were included in the retrospective study, and their MRI spine and bone scans were analysed.ResultsTen patients were detected to have definite spinal metastasis by bone scan, whereas 12 patients had definite skeletal metastasis by MRI spine. Compared with the ‘gold standard’, derived from clinical and radiological follow-up, the sensitivities for radionuclide bone scan and that for MRI spine for detecting skeletal metastasis were 71.4 and 85.7%, respectively (P = 0.023), whereas the specificities were 96.5 and 97.7%, respectively (P = 0.95). Of the 34 individual metastatic lesions in the spine, 15 were concordantly positive on both scans, whereas five lesions were positive only by bone scan and 11 positive only by MRI. The addition of MRI spine in the staging for prostate cancer resulted in a change of stage and management plan in seven (7%) patients.ConclusionMRI spine has comparable specificity and slightly better sensitivity than bone scan to detect spinal metastasis from prostate cancer.     

Factors influencing the use of single vs multiple fractions of palliative radiotherapy for bone metastases: a 5-year review

AimsEvidence from a number of randomised trials and meta-analyses supports the use of single-fraction radiotherapy for the palliation of painful bone metastases. This study explores patient and treatment factors that influence the choice of single compared with multiple-fraction radiotherapy for the treatment of bone metastases in clinical practice.Materials and methodsThe Princess Margaret Hospital Palliative Radiation Oncology Program Database served as the basis for our report. All courses of treatment delivered for bone metastases were extracted. Courses were classified into single or multiple fractions. Clinical characteristics were compared between the two groups.ResultsBetween 1998 and 2002, 882 courses of radiotherapy were delivered for the treatment of bone metastases, of which 283 (32%) were a single fraction. The proportion of single-fraction treatments was 37% in 1998, 30% in 1999 and 43% in 2000, but dropped to 26% and 28% in 2001 and 2002, respectively (P = 0.02). Patients treated with single fractions were significantly older (68 ± 12 years vs 64 ± 12 years), and had more weight loss and poor performance status. Single fractions included 20% of treatments in palliative irradiation of the spine, 36% in the pelvis and long bones, and 59% in the chest wall (P < 0.001). There was no significant difference in patients' gender, primary cancers, number of metastatic sites, treating physicians, enrollment in a clinical trial and general radiotherapy waiting time in our department. Multivariate analysis indicated age (P = 0.001), performance status (P < 0.001), anatomical site (P < 0.001) and year of radiotherapy (P = 0.006) as significant.ConclusionOne-third of palliative radiotherapy courses for bone metastases in our programme were given as single fractions. Performance status, age and anatomical site were significant factors affecting single compared with multiple fractionation. The variation in the use of single fractions over time may reflect the dynamic process of interpretation and application of evidence from clinical trials to practice.     

Subanaesthetic ketamine spares postoperative morphine and controls pain better than standard morphine does alone in orthopaedic-oncological patients

BackgroundPostoperative pain in patients with bone and soft tissue cancer is different from that of other surgical patients due to the severity of the pain generated during surgery and because many of them have already been in pain preoperatively. The search for optimal intravenous pharmacologic management for this population is an ongoing one. We conducted a 10-month prospective, randomised, double blind study to compare the effects of a standard morphine dose to a 35%-lower dose plus a subanaesthetic dose of ketamine for postoperative pain control in patients undergoing bone and soft tissue cancer surgery under standardised general anaesthesia.MethodsAfter extubation, when objectively awake (⩾5/10 on a 0–10 visual analogue scale (VAS)) and complaining of pain (⩾5/10 VAS), patients were connected to an intravenous patient-controlled analgesia (IV-PCA) device that delivered 1.5 mg morphine/bolus (MO group) or 1 mg morphine + 5mg ketamine/bolus (MK group), with a 7 min lockout time. Rescue intramuscular diclofenac 75 mg was available Q4/day. Follow-up lasted 96 h.ResultsFifty-seven patients (24 males, aged 18–74 years) completed the study. Pain scores were lower in the MK group compared to the MO patients, although MO patients (n = 29) used 32.9 ± 24.9 mg/patient morphine during the first 24 postoperative h compared to 14.6 ± 11.4 mg/patient (P < 0.05) for the MK patients (n = 28). At that time point, 11 MO versus 4 MK patients still required IV-PCA (P < 0.05). Diclofenac was also used more in the MO group. All vital signs were similar between the groups. The physiotherapy score was 35% higher for the MK patients (P < 0.05). No patient had hallucinations. Postoperative nausea and vomiting rates were higher in the MO group.ConclusionsThe use of subanaesthetic ketamine plus 2/3 the standard dose of morphine following bone and tissue resections results in 1) lower and more stable pain score, 2) ∼60% morphine sparing effect, 3) a shorter period of postoperative IV-PCA dependence. Such therapy is also associated with better early physical performance.     

Is the prognosis of stage 4s neuroblastoma in patients 12 months of age and older really excellent?

PurposeIn the International Neuroblastoma Risk Group (INRG) classification system, stage 4s was changed into stage MS in children less than 18 months of age. Stage MS is defined as a metastatic disease with skin, liver and bone marrow, similar to INSS stage 4s. To evaluate the outcome of stage 4s cases in patients 12 months of age and over and to determine the appropriate treatment strategy.MethodWe performed a retrospective review of 3834 patients registered with the Japanese Society of Pediatric Oncology and Japanese Society of Pediatric Surgeons between 1980 and 1998.ResultsThe rates of stage 4s patients were 10.7%, 6.3% and 3.3% in patients of ⩽11 months of age, from ⩾12 to ⩽17 months of age, ⩾18 months of age, respectively. The 5 year event-free survival rates were 89.4%, 100% and 53.1%, respectively. The rates of MYCN amplification and unfavourable histology were smaller in stage 4s groups than stage 4 groups in all ages.ConclusionIn the children 12 months of age and older, stage 4s cases are markedly different from stage 4 cases in regard to the clinical features and prognosis. The prognosis of stage 4s cases from ⩾12 to ⩽17 months of age is excellent. The concept of stage MS appears to be appropriate.     

Evaluation of morphological/immunohistochemical versus nuclear medicine imaging modalities in detecting metastatic bone and/or marrow deposits in neuroblastoma patients

Background &; PurposeIn planning diagnostic or follow-up investigational strategies, neuroblastoma (NB) metastatic deposits in bone and/or bone marrow (BM) should be detected as early as possible. Therefore, all investigational detection tools should be conducted simultaneously for precise staging. However, because of the financial conditions in our developing countries and in view of the cost/benefit relationship, the question is, can one detection tool only become satisfactory and replacing others? The purpose of our study is to compare simultaneous results of bone and metaiodobenzylguanidine (MIBG) scans versus BM biopsies with immunohistochemical (IHC) staining; in detecting bone and/or BM metastatic deposits in NB patients.Material and methodsThis study included 138 NB patients; 46 were de novo and 92 were under follow-up. They were subjected to bilateral BM biopsies, IHC staining (using NSE McAb) and Tc-99m methylene diphosphonate (Tc-99m MDP) bone scan (BS). Only 57/138 patients were, in addition, subjected to I-131 MIBG scan.ResultsMatched results between IHC-stained BM sections and bone scans (BSs) 107/138 (77.5%) were higher than the un-matched ones 31/138 (22.5%). There was a moderate agreement between the two methods in all studied cases (Kappa = 0.538) and it was higher among de novo (Kappa = 0.603) than follow-up group (Kappa = 0.511). Among the 31 un-matched results, the most frequent (17/31) were due to the presence of minute amount of infiltrating NB cells that could be detected by IHC-stained BM sections and not by BSs. The less frequent (12/31) were due to the presence of metastatic deposits outside pelvic bones that could be detected by BSs and not by IHC-stained BM sections mainly in the follow-up cases (11/12) rather than de novo cases (1/12). The matched results between IHC-stained BM sections and MIBG scans 54/57 (94.7%) were higher than the un-matched ones 3/57 (5.3%). The agreement between the two methods was higher among de novo (Kappa = 1.000) than follow-up group (Kappa = 0.847). The agreement between IHC-stained BM sections and MIBG scans was substantial (Kappa = 0.890) while that between IHC-stained BM sections and BSs was moderate (Kappa = 0.538).ConclusionsWe suggest a step-wise strategy to be applied, at least in developing countries, in approaching de novo and follow-up NB cases for detecting bone and/or BM metastatic deposits. This strategy might be beneficial if it is considered during application of NB guide-lines for diagnosis and follow-up.     

Single French centre retrospective analysis of local control after high dose radiotherapy with or without chemotherapy and local control for Pancoast tumours

PurposeSuperior sulcus non-small cell lung cancer represents less than 5% of all lung cancers and is a challenge for the physicians because of clinical presentation, treatments related toxicities and poor prognosis. The aim of this preliminary retrospective report is to present outcomes of patients affected by a superior sulcus non-small cell lung cancer, treated by high dose radiotherapy (> 60 Gy) with or withour chemotherapy.Patients and methodsAll adult inoperable or unresectable patients (≥ 18 years) with a clinical and radiological diagnosis of superior sulcus non-small cell lung cancer treated in our department by radiotherapy with or without chemotherapy were retrospectively analysed. Primary endpoint was the local control. Overall survival, metastasis free survival and toxicity rates were also analysed and reported.ResultsFrom January 1999 to June 2009, 12 patients were treated by exclusive high-dose radiochemotherapy. Median age was 53 years (range: 33–64 years); mean follow-up time was 20 months (range: 2–75 months). Mean local control, overall survival and metastasis free survival were 20.2, 22 and 20 months, respectively. At the time of this analysis, seven patients died of cancer and three of them presented only a metastatic disease progression. One patient died of acute cardiac failure 36 months after the end of radiochemotherapy and was disease free. Treatment was well tolerated and any acute and/or late G3-4 toxicity was recorded (NCI-CTC v 3.0 score).ConclusionThis analysis confirms the interest of exclusive high-dose radiochemotherapy in treating inoperable superior sulcus non-small cell lung cancer patients, in achieving good local control and overall survival rates.     

Impact of age on choice of chemotherapy and outcome in advanced colorectal cancer

BackgroundAge is a major risk factor for development of sporadic colorectal cancer but elderly patients are underrepresented in clinical trials and are potentially offered chemotherapy less often.MethodsData were obtained from South Australian Clinical Registry for advanced colorectal cancer between 1st February 2006 and 9th September 2010. Patients who received chemotherapy were analysed to assess the impact of single versus combination chemotherapy and to assess the outcome in two age cohorts, age <70 years and ⩾70 years.ResultsOut of a total of 1745 patients in the database during this time period, 951 (54.5%) received systemic chemotherapy. 286 (30%) received first line therapy (median age 74 years) with single agent fluoropyrimidine and 643 patients (68%) received first line combination chemotherapy (median age 64 years). The median overall survival of patients receiving first line combination chemotherapy was 23.9 months compared to 17.2 months for those who received single agent fluoropyrimidine (p < 0.001). Combination chemotherapy was given to 81% of patients aged <70 years compared to 53% of those ⩾70 years. There was no significant difference in median overall survival of patients receiving chemotherapy by age cohort, 21.3 months for age <70 years and 21.1 months for age ⩾70 years (p = 0.4).ConclusionTreatment outcomes are comparable in both the elderly and younger patients. Patients who received initial combination chemotherapy were younger and had a longer median overall survival. In our study, age appeared to influence the treatment choices but not necessarily outcome.     

Sarcomas and malignant phyllodes tumours of the breast--a retrospective study

BackgroundAlthough most breast cancers are adenocarcinomas of the mammary gland, primary breast sarcomas may also arise from mammary gland mesenchymal tissue. The annual incidence of primary breast sarcoma is low and has been estimated at 45 new cases per 10 million women. These tumours are at high risk of recurrence and are known to have poor prognosis. Phyllodes tumours represent a specific subset of these breast soft tissue tumours. They are composed of a connective tissue stroma and epithelial elements. Pathological presentation ranges from grade I to malignant phyllodes tumours (grade III) where the stromal component clearly exhibits a sarcoma pattern.Materials and MethodsSAPHYR (SArcoma and PHYllode Retrospective) is a retrospective study of the experience of Leon Bérard Cancer Centre (Lyon, France) from 1966 to August 2004. SAPHYR aims to describe the characteristics of primary breast sarcomas and to define potential survival factors to be evaluated in future prospective studies.ResultsWe included 70 patients. Half of them presented at least one recurrence (35/70). Median disease-free-survival (DFS) was 1.15 years. At 3 years, median overall survival had not been reached and more than 61% of the patients were alive. Quality of surgical resection was significantly (p = 0.036) different whether patients were in the R0 group (72%) or not (38%). No survival difference was found between malignant phyllodes (grade III) and other primary breast sarcomas (angiosarcomas excluded). Histology revealed three significantly (p = 0.0003) different prognostic groups: phyllodes grade I and II (DFS = 57%), angiosarcomas (DFS = 7%) and phyllodes grade III and other primary breast sarcomas (DFS = 45%).DiscussionPhyllodes tumours and primary breast sarcomas are totally different from epithelial breast cancers and should be considered as a distinct group of rare tumours. The first goal of treatment is to achieve negative margins (R0). We propose to treat the patients according to the clinical practice guidelines in use for soft tissue sarcomas and address them to a reference centre for sarcoma. Treating rare tumours in the same place should permit us to standardise pathological data and to include patients into multicentric radiotherapy or chemotherapy protocols to improve overall survival. As further prospective studies are needed, European oncology groups must join their forces to create a prospective Rare Cancer Network.     

Resumption or persistence of menstruation after cytotoxic chemotherapy is a prognostic factor for poor disease-free survival in premenopausal patients with early breast cancer

BackgroundWe investigated the relationship between resumption or persistence of menstruation after cytotoxic chemotherapy (RM) and disease-free survival (DFS) in premenopausal patients with early breast cancer.MethodsMedical records from 872 patients who received cytotoxic chemotherapy for stage I to III breast cancer were retrospectively reviewed.ResultsThe median patient age was 41 years (range, 21–54) and the median follow-up duration was 6.2 years (range, 0.7–10.4). Six hundred ninety-two patients (79.4%) were hormone receptor (HR) positive and the majority of these received tamoxifen therapy after completing chemotherapy. The chemotherapy-induced amenorrhea (CIA) rate was 76.7% (n = 669), and 51.8% (n = 452) experienced RM during the follow-up period. One hundred twenty-one (13.9%) patients had persistent menstruation without CIA. DFS was significantly affected by younger age at diagnosis (≤35 years) (P = 0.013), tumor size > 2 cm (P < 0.001), node positivity (P < 0.001), HR negativity (P < 0.001), HER2 positivity (P = 0.010), and RM (P < 0.001). HR negativity [hazard ratio 1.7, 95% confidence interval (CI) 1.2–2.4, P = 0.006], tumor size > 2 cm (hazard ratio 2.1, 95% CI 1.4–3.0, P < 0.001), node positivity (hazard ratio 3.0, 95% CI 2.0–4.7, P < 0.001), and RM (hazard ratio 1.8, 95% CI 1.2–2.7, P = 0.004) remained significant factors for DFS on multivariate analysis.ConclusionsA considerable proportion of premenopausal patients treated with chemotherapy experienced RM after CIA. RM was a poor prognostic factor for DFS in premenopausal patients with early breast cancer.     

Characteristics and outcome of patients with ganglioneuroblastoma, nodular subtype: a report from the INRG project

AimDescribe characteristics and outcome of INRG patients with ganglioneuroblastoma, nodular subtype (GNBn).Patients and methodsAmongst 4071 patients in the INRG database with known INPC histological category, 232 patients with GNBn were identified. Patients were categorised by clinical, pathological and genetic characteristic. For event-free survival (EFS) and overall survival (OS), Kaplan–Meier curves and lifetables were generated, and the outcome of subgroups was compared using log rank test.ResultsPatients with GNBn were older (83% >18 months), a higher proportion had unfavourable INPC pathology (83%), and rarely had MYCN gene amplified tumours (2%). Otherwise, the distribution of clinical and biological risk factors including stage, ferritin, initial treatment, grade of NB differentiation, MKI, 11q, 1p, and 17q were similar between patients with GNBn and the overall INRG cohort. EFS and OS were 54% ± 5% and 68% ± 5%, respectively. A cohort with superior outcome was identified: OS for GNBn patients younger than 18 months was 95% ± 5% (n = 39) and for GNBn patients with stage 1, 2, 3, 4s was 95% ± 3% (n = 125). Conversely, a poor outcome sub-group could also be identified: OS for stage 4 was 35% ± 7% (n = 107).ConclusionsPatients with GNBn tumours are rare and have a very heterogeneous outcome. Except for LDH and MKI, the factors prognostic in the overall NB cohort are also prognostic in patients with GNBn. Similar to the overall NB cohort, patients with GNBn older than 18 months of age, with stage 4 disease represent a high-risk sub-group and should be considered for aggressive treatment upfront.