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1.
J Gastrointest Cancer ; 48(1): 1-7, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27412395

ABSTRACT

PURPOSE: The aim of this study is to determine overall survival, disease-specific survival and stoma-free survival after treatment of squamous cell carcinoma of the anus with chemoradiotherapy followed by brachytherapy or electron boost in a recent cohort of patients. METHODS: Fifty-two patients (median age 62 years) were treated with radical chemoradiotherapy (mitomycin C, infusional 5-fluorouracil concurrently with conformal radical radiotherapy 45 Gy in 25 fractions over 5 weeks) followed by a radiotherapy boost between 1 December 2000 and 30 April 2011. Follow-up was to 30 November 2014. Thirty-six patients received a boost (15-20 Gy) over 2 days with 192Ir needle brachytherapy for anal canal tumours, and 16 patients received electron beam therapy (20 Gy in 10 fractions in 2 weeks) for anal margin tumours. A defunctioning stoma was only created prior to chemoradiotherapy for fistula or severe anal pain. RESULTS: The overall survival for the 36 patients treated with chemoradiotherapy followed by brachytherapy was 75 % (95 % CI, 61-89) at 5 years, the disease-specific survival was 91 % (95 % CI, 81-101 %), and the stoma-free survival was 97 % (95 % CI, 91-103 %) all at 5 years. For the 16 patients treated with an electron boost for anal margin tumours, the 5-year overall survival, disease-specific survival and stoma-free survival were 68 % (95 % CI, 44-92 %), 78 % (95 % CI, 56-100 %) and 80 % (95 % CI, 60-100 %), respectively. CONCLUSIONS: A very low stoma formation rate can be obtained with radical chemoradiotherapy followed by a brachytherapy boost for squamous cell carcinoma of the anal canal but not with an electron boost for anal margin tumours.


Subject(s)
Anus Neoplasms/drug therapy , Anus Neoplasms/radiotherapy , Brachytherapy/methods , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Anus Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy , Colostomy , Electrons , Female , Humans , Male , Middle Aged , Survival Analysis , Tomography, X-Ray Computed
2.
Pediatr Obes ; 11(5): 349-53, 2016 10.
Article in English | MEDLINE | ID: mdl-26317846

ABSTRACT

BACKGROUND: Individuals with metabolically healthy obesity (MHO) do not have the metabolic complications usually associated with obesity. OBJECTIVE: To examine whether youth adiposity, or change in adiposity from youth to adulthood, predicts MHO 20 years later. METHODS: A national sample of 2410 Australian participants had height, weight and waist circumference (WC) measured in 1985 (7-15 years old) and 2004-2006 (26-36 years old). A fasting blood sample was taken in 2004-2006. MHO was defined as body mass index (BMI) ≥30 kg m(-2) , normal fasting glucose (<5.6 mmol L(-1) ), triglycerides (<1.695 mmol L(-1) ), high-density lipoprotein-cholesterol (>1.036 mmol L(-1) men, > 1.295 mmol L(-1) women), blood pressure (<130/85 mmHg) and no medication for these conditions. Relative risks (RR) were calculated using log binomial regression and expressed per unit of youth BMI (or WC) z-score or change in BMI (or WC) z-score from youth to adulthood, adjusted for sex and youth age. RESULTS: In total 323 individuals were obese at follow-up, 79 (24.5%) were MHO. Adult MHO was not associated with youth BMI (RR: 1.00, 95%CI: 0.85-1.19) or WC (RR: 0.93, 95%CI: 0.79-1.11). Individuals were less likely to be MHO if they had larger increases in BMI (BMI RR: 0.74, 95%CI: 0.57-0.97) or WC (RR: 0.70, 95%CI: 0.55-0.90) from youth to adulthood. CONCLUSIONS: Change in adiposity from youth to adulthood predicted adult MHO better than youth adiposity alone.


Subject(s)
Adiposity/physiology , Obesity, Metabolically Benign/physiopathology , Adolescent , Adult , Australia , Blood Glucose , Body Mass Index , Child , Female , Humans , Lipids/blood , Male , Waist Circumference
4.
Clin Oncol (R Coll Radiol) ; 26(4): 197-202, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24485884

ABSTRACT

AIMS: The pathology of tumours after chemo/radiotherapy for locally advanced rectal cancer can be difficult to interpret. The ypTNM staging does not accurately predict outcomes. Therefore, we developed a new prognostic index for this purpose. MATERIALS AND METHODS: The Nottingham Rectal Cancer Prognostic Index (NRPI) is based on a study of 158 patients with locally advanced rectal cancer treated with preoperative chemo/radiotherapy at Nottingham University Hospital between April 2001 and December 2008. Patients were treated with radiotherapy to a dose of 50 Gy in 25 fractions over 5 weeks with/without concurrent capecitabine chemotherapy. Surgery was carried out after an interval of 6-10 weeks. Factors found to be significant on univariate analysis to predict for disease-free (DFS) and overall survival were further explored in multivariate analysis. The significant factors (Mandard tumour regression grade, perineural invasion, circumferential resection margin status and nodal status) were weighted to establish a score for the index. The median follow-up was 40 months (range 3-90 months). RESULTS: On survival analysis, four distinct prognostic groups were found: Score 0 = excellent prognosis, 1-3 = good prognosis, 4-8 = moderate prognosis, 9-14 = poor prognosis. The NRPI significantly predicted both DFS and overall survival (P < 0.0001). DFS at 5 years was 95, 63, 25 and 0% for the four groups. On multivariate analysis the NRPI was found to be the strongest predictor of DFS including nodal and circumferential resection margin status (P < 0.0001). It was a stronger predictor of overall survival than the American Joint Committee on Cancer/Dukes staging (P < 0.0001). CONCLUSIONS: The NRPI allocates patients into distinct prognostic categories. This seems to be a much stronger predictive factor than the American Joint Committee on Cancer/Dukes staging. This requires further validation, but seems to be a useful clinical index for future studies.


Subject(s)
Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery , Rectum/injuries , Survival Rate , Treatment Outcome
5.
Br J Dermatol ; 167(5): 1118-23, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22759204

ABSTRACT

BACKGROUND: Primary cutaneous B-cell lymphomas (PCBCL), with the exception of large B-cell lymphoma of leg type and intravascular large B-cell lymphoma, are associated with an excellent prognosis. These lymphomas have become much better understood in recent years leading to the publication in 2005 of the World Health Organization-European Organisation for Research and Treatment of Cancer classification. OBJECTIVES: To determine the relative frequency of occurrence of subtypes of PCBCL in a defined population, and the survival of patients with these subtypes. METHODS: During the period 1987-2009, 61 consecutive patients with PCBCL were identified from the Nottingham Lymphoma Registry (population 1·1 million). After histological review, the number of patients with each subtype was as follows: marginal zone, 18; follicle centre, 14; diffuse large B cell, leg type, 16; diffuse large B cell, other sites, 12; and intravascular large B cell, one. RESULTS: The 5- and 10-year lymphoma-specific survival for patients with marginal zone lymphoma was 100%. The only patient with intravascular large B-cell lymphoma died from widespread disease in spite of chemotherapy. The 4-year lymphoma-specific survival for follicle centre cell lymphoma was 90%. Patients with the other subtypes had the following 5-year lymphoma-specific survival rates: diffuse large B cell, leg type, 61% and diffuse large B cell, other, 40%. The median age at diagnosis for patients with diffuse large B-cell lymphoma, leg type was 82 years and as a consequence the 5-year overall survival was only 15%. There was a 3·4-fold increase in the incidence of PCBCL from the period 1987-1997 to the period 1998-2009. CONCLUSIONS: PCBCL is a rare disease (incidence around three per million population per year). It is, in our view, essential that it is diagnosed by a pathologist with an interest in cutaneous lymphoma and that the very different prognosis of the individual subtypes is appreciated by the treating clinician.


Subject(s)
Lymphoma, B-Cell/diagnosis , Skin Neoplasms/diagnosis , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Lymphoma, B-Cell/classification , Lymphoma, B-Cell/mortality , Male , Middle Aged , Prognosis , Skin Neoplasms/classification , Skin Neoplasms/mortality , Survival Rate , United Kingdom , World Health Organization
6.
J Surg Oncol ; 106(6): 748-52, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22674046

ABSTRACT

BACKGROUND: The MAGIC trial demonstrated the perioperative regimen of Epirubicin (E), Cisplatin (C) and 5-Fluorouracil (F) to have an overall survival benefit for patients with gastro-esophageal adenocarcinomas. We present our experience of the peri-operative regimen of ECF/ECX(X = Capecitabine) in operable gastro-esophageal adenocarcinoma. METHODS: Analysis of retrospective data of patients treated with MAGIC style therapy between May 2006 and August 2008 with potentially operable gastro-esophageal adenocarcinoma. RESULTS: One hundred patients underwent peri-operative chemotherapy according to the MAGIC protocol. Median age was 66 years, with 39% above the age of 70 years. The tumours were evenly distributed between the lower esophagus, gastro-esophageal junction and stomach. Seventy-nine percent completed all pre-operative cycles of chemotherapy and 81% proceeded to surgery, whilst 24% did not receive curative surgery. The median survival on an intention to treat analysis is 31.7 months from diagnosis. The median survival of patients who underwent resection has not yet been reached after a median follow-up of 41.4 months. CONCLUSION: Our patient population is older than the patients in the MAGIC trial (age 66 years vs. 62 years) with a much higher proportion of esophageal and GEJ tumours. Overall, curative resection rate was comparable to the MAGIC trial. Overall survival is superior to that found in the MAGIC trial.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/drug therapy , Esophagogastric Junction , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Female , Humans , Male , Middle Aged , Retrospective Studies
7.
Br J Cancer ; 107(3): 531-6, 2012 Jul 24.
Article in English | MEDLINE | ID: mdl-22713660

ABSTRACT

BACKGROUND: The Nottinghamshire Lymphoma Registry contains the details of all the patients diagnosed with lymphoma (since 1 January 1973) within a defined geographical area with a population of 1.1 million. It was therefore possible to study the outcome of treatment for Hodgkin's disease for three 10-year cohorts (1973-1982, 1983-1992 and 1993-2002).The aims of the study were to compare survival time among the three patient cohorts, to identify prognostic factors and to estimate relative survival. METHODS: A total of 745 patients diagnosed between 1973 and 2002 were analysed for survival. Survivorship was estimated by the Kaplan-Meier method and parametric survival models. An accelerated failure-time regression was used for multivariate analysis. RESULTS: Overall, patients were observed for 9.8 (0.3-34.82) years (median(range)), on average. One, five and fifteen-year disease-specific survival was found to be 87% (85-90%), 77% (74-80%) and 70% (67-74%), respectively. For those for diagnosed between 1973 and 1982, the 15-year survival was found to be 57%; for 1983-1992, it was 74% and for 1993-2002, it was 83% (P<0.001). The difference remained significant after adjusting for prognostic factors. The actuarial risk of developing a second malignancy at 20 years was for the 1973-1982 cohort, 12.4%, and for the 1983-1992 cohort, 18.8%. CONCLUSION: Treatment advances and effective management of toxicities of treatment over time, have resulted in a significantly longer survival for patients with Hodgkin's disease diagnosed within a defined population.


Subject(s)
Hodgkin Disease/mortality , Survivors/statistics & numerical data , Adult , Aged , Cohort Studies , Female , Hodgkin Disease/drug therapy , Humans , Male , Middle Aged , Neoplasms, Second Primary/drug therapy , Neoplasms, Second Primary/epidemiology , Neoplasms, Second Primary/mortality , Prognosis , Survival Rate , United Kingdom/epidemiology
8.
Eur J Cancer ; 47(8): 1138-45, 2011 May.
Article in English | MEDLINE | ID: mdl-21220198

ABSTRACT

PURPOSE: To assess the prognostic value of the Mandard tumour regression score (TRG) following pre-operative chemo/radiotherapy in patients with locally advanced rectal cancer. METHODS AND MATERIALS: The study involved 158 patients with locally advanced rectal cancer treated with pre-operative long course chemo/radiotherapy at Nottingham University Hospital between April 2001 and December 2008. Patients were treated with radiotherapy to a dose of 50 Gy in 25 fractions over 5 weeks with or without concurrent capecitabine chemotherapy at a dose of 1650 mg/m(2)/day. Surgery was normally performed after an interval of 6-10 weeks. The response to pre-operative treatment was carefully graded by a single pathologist using the five point Mandard score. The median follow-up was 40 months (range 3-90 months). RESULTS: Of the 158 patients 14% were TRG1, 41% were TRG2, 31% were TRG3, 13% were TRG4 and 1% were TRG5. The groups were combined into TRG1, TRG2 and TRG3-5 to simplify further analysis. The Mandard score was clearly related to both disease-free (p < 0.001) and overall survival (p = 0.012). On multivariate analysis perineural invasion, nodal status, TRG and circumferential resection margin status were the most powerful predictors of disease-free survival. CONCLUSIONS: The Mandard tumour regression score is an independent prognostic factor and predicts for long-term outcome following pre-operative chemo/radiotherapy in rectal cancer.


Subject(s)
Rectal Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Dose-Response Relationship, Radiation , Drug Therapy/methods , Humans , Middle Aged , Multivariate Analysis , Neoplasm Staging/methods , Prognosis , Proportional Hazards Models , Radiotherapy/methods , Rectal Neoplasms/therapy , Treatment Outcome
9.
BMJ Case Rep ; 20112011 Mar 03.
Article in English | MEDLINE | ID: mdl-22707632

ABSTRACT

The authors present the first reported case of primary cutaneous marginal zone B cell lymphoma (PCMZL) in monozygotic twins. The occurrence of PCMZL in monozygotic twins is likely to be due to a combination of shared genetic and environmental factors. A different treatment modality was used to treat each patient but both achieved a complete clinical response.


Subject(s)
Diseases in Twins/pathology , Lymphoma, B-Cell, Marginal Zone/pathology , Skin Neoplasms/pathology , Humans , Male , Middle Aged , Twins, Monozygotic
10.
Clin Oncol (R Coll Radiol) ; 21(1): 23-31, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19027272

ABSTRACT

AIMS: To determine tumour regression (volume-halving time) obtained after chemo/radiotherapy, and thereby the ideal interval between the start of treatment and surgery in order to obtain a high rate of complete response. MATERIALS AND METHODS: In total, 106 patients with cT3,4 rectal cancer who received preoperative radiotherapy alone or concurrently with capecitabine chemotherapy at Nottingham City Hospital, UK were studied. The rectal tumour volume visible on the computed tomography planning scan was compared with the residual pathological volume and the tumour volume-halving time calculated. The radiotherapy response was graded according to the Mandard system. RESULTS: Fifty-three patients had radiotherapy alone, with 53 patients having concurrent chemoradiotherapy. The median tumour volume-halving time was found to be 14 days and not influenced by the addition of chemotherapy. The Mandard score, the interval from the start of treatment to surgery and the tumour volume-halving time were statistically associated with tumour regression. The median tumour volume in our series of 54 cm(3) would require an interval of 20 weeks after the start of treatment to surgery to regress to <0.1 cm(3) (10 volume-halving times; 140 days). CONCLUSIONS: The initial tumour volume and median volume-halving time provide the best estimates for determining the optimum length of interval between the completion of preoperative chemo/radiotherapy and surgery in locally advanced rectal cancer.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Neoadjuvant Therapy , Rectal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Capecitabine , Deoxycytidine/therapeutic use , Female , Fluorouracil/therapeutic use , Humans , Male , Middle Aged , Radiotherapy, Conformal , Rectal Neoplasms/drug therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/radiotherapy
11.
Bone Marrow Transplant ; 32(8): 759-61, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14520418

ABSTRACT

We report three cases of massive chest wall plasmacytoma, each greater than 10 cm in diameter, without evidence of overt myeloma, whom we treated with a combination of VAD chemotherapy consolidated by high-dose melphalan and autologous peripheral blood stem cell transplantation and radical radiotherapy. All three patients completed all components of their therapy without experiencing any major side effects and one patient has had a durable remission. The other two patients have had disease progression but at sites other than the original tumour.


Subject(s)
Antineoplastic Agents, Alkylating/administration & dosage , Hematopoietic Stem Cell Transplantation , Melphalan/administration & dosage , Plasmacytoma/drug therapy , Soft Tissue Neoplasms/drug therapy , Combined Modality Therapy , Humans , Male , Middle Aged , Plasmacytoma/radiotherapy , Remission Induction , Soft Tissue Neoplasms/radiotherapy , Thoracic Wall
12.
Bone Marrow Transplant ; 31(3): 157-61, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12621475

ABSTRACT

Allogeneic SCT for myeloma may be curative for young patients, but its role remains controversial because of a reported high TRM in some series. Since 1991, we have performed 25 allografts for myeloma using fully matched sibling donors. Of the 18 evaluable patients, 13 achieved CR at a median time of 2.5 months post-transplant. The five patients who were not in CR when assessed at 3 months received a short course of alpha-interferon and four subsequently achieved CR with this approach at a median of 82 days. One patient who failed to respond to IFN went on to achieve CR after four doses of DLI therapy, thus giving an overall CR rate of 72%. Seven patients have relapsed at a median of 4.7 years post-transplant (range 1.38-7.7 years) including two patients who had received IFN therapy. In five of these cases, relapse has been as a localised area of bone disease or isolated plasmacytoma with no evidence of marrow involvement by trephine biopsy or molecular analysis. All patients with localised relapse were treated with local radiotherapy +/-DLI and four are currently disease free despite two patients having had further treatment for a second localised lesion. Six patients died of TRM (24%) and the OS at 8 years is currently 69% with an EFS of 26%. These results suggest that allogeneic SCT for myeloma can be carried out with an acceptable TRM and a high CR rate. However, late relapses as localised disease may be a frequent finding and may represent foci of myeloma not eradicated by the conditioning. The use of pretransplant MRI scanning and top-up radiotherapy to involved areas may be useful in preventing this type of relapse.


Subject(s)
Bone Marrow Transplantation/physiology , Multiple Myeloma/therapy , Stem Cell Transplantation , Adult , Bone Marrow Transplantation/immunology , Bone Marrow Transplantation/mortality , Disease-Free Survival , Female , Graft vs Host Disease/epidemiology , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Plasmacytoma/therapy , Recurrence , Retrospective Studies , Stem Cell Transplantation/adverse effects , Stem Cell Transplantation/mortality , Survival Rate , Time Factors , Transplantation Conditioning/methods , Transplantation, Homologous/immunology , Transplantation, Homologous/mortality , Treatment Outcome
13.
Ann Oncol ; 14(2): 258-67, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12562653

ABSTRACT

BACKGROUND: The aim of this study was to determine in a randomised trial whether there is any significant difference in toxicity between modified CHOP and MCOP chemotherapy in elderly patients with aggressive non-Hodgkin's lymphoma (NHL) and to determine whether this reduced dose chemotherapy can be administered with full dose intensity, low toxicity and produce acceptable survival. PATIENTS AND METHODS: Between 1993 and 2000, 155 eligible patients were randomised into this trial mainly from three centres (Nottingham, Birmingham and Leeds, UK). The patients were newly diagnosed with aggressive NHL and had a median age of 74 years (range 65-91 years). Ninety-six patients (62%) had bulky stage I or II disease; 59 patients (38%) had either stage III or IV disease; 77% had one or more extranodal sites involved at presentation; and 31% showed B symptoms. Seventy-seven patients were randomised to receive six cycles of modified CHOP (cyclophosphamide 600 mg/m(2) i.v., doxorubicin 30 mg/m(2) i.v., vincristine 1 mg i.v. all on day 1 with prednisolone 20 mg bd for days 1-5) every 21 days and 78 patients to MCOP (mitozantrone 10 mg/m(2) i.v. substituted for doxorubicin). Growth factors were not used routinely. After completion of chemotherapy, 39 patients received involved field radiotherapy (35-40 Gy) in 20 fractions. RESULTS: One hundred and one patients (65%) completed all six cycles of chemotherapy. The median course dose intensity was 97%. The median follow-up for 53 surviving patients was 51 months. The median survival was 19 months (95% confidence interval 10-36 months) with an actuarial survival of 47% at 2 years and 42% at 3 years (CHOP versus MCOP, P = 0.79). There was no significant difference in any of the toxicities experienced with either CHOP or MCOP, except for white cell count (46 patients on MCOP and 27 patients on CHOP had grade 3 or 4 toxicity, P = 0.002) and red cell transfusion (37 patients, MCOP; 17 patients, CHOP; P = 0.001). Grade 3 or 4 neutropenia was documented in 75 patients (50%). One patient died from toxicity whilst in remission and seven patients died with septicaemia and persistent NHL. CONCLUSION: This multicentre randomised trial provides further information on the dose intensity achievable with CHOP or MCOP regimens in elderly patients (median age 74 years) with aggressive NHL. These dose-reduced regimens can be given with nearly 100% dose intensity with 65% of patients completing all the treatment. Survival is comparable to that observed with the more intensive regimens given in this age group.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Administration, Oral , Age Factors , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Combined Modality Therapy , Cyclophosphamide/administration & dosage , Dose-Response Relationship, Drug , Doxorubicin/administration & dosage , Female , Humans , Infusions, Intravenous , Lymphoma, Non-Hodgkin/pathology , Lymphoma, Non-Hodgkin/radiotherapy , Male , Mitoxantrone/administration & dosage , Prednisolone/administration & dosage , Prednisone/administration & dosage , Survival , Treatment Outcome , Vincristine/administration & dosage
14.
J Clin Oncol ; 20(1): 231-6, 2002 Jan 01.
Article in English | MEDLINE | ID: mdl-11773174

ABSTRACT

PURPOSE: To assess the effect of a reduced dose of radiotherapy (RT) in patients with primary CNS lymphoma (PCNSL) responding to the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) regimen. PATIENTS AND METHODS: Patients received one cycle of CHOD and two of BVAM. In the first trial, all 31 patients received 45-Gy whole-brain RT (CHOD/BVAM I). In the second, with 26 patients, RT dose was reduced to 30.6 Gy if there was a complete response (CR) after chemotherapy (CHOD/BVAM II). RESULTS: Age, performance status, and chemotherapy received were similar in both protocols. CR rate at the end of all treatment was 68% for CHOD/BVAM I and 77% and for CHOD/BVAM II. Treatment modality was the only predictor of relapse, with 3-year relapse risks of 29% and 70% for CHOD/BVAM I and II, respectively. This was specifically important in the 25 patients less than 60 years old (3-year relapse risk, 25% v 83%; P =.01). The 5-year overall survival (OS) was 36%. Age (< 60 v > or = 60 years) was the only predictor for OS in the multivariate analysis (relative risk, 2.1; 95% confidence interval, 1.4 to 2.8). RT dose was the only predictor of OS in patients younger than 60 years old who achieved CR at the end of all treatment (3-year OS, 92% v 60% for patients receiving 45 or 30.6 Gy, respectively; P =.04). CONCLUSION: Reduction of the RT dose from 45 Gy to 30.6 Gy in patients younger than 60 years old with PCNSL who achieved CR resulted in an increased risk of relapse and lower OS.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/radiotherapy , Cranial Irradiation/methods , Lymphoma/radiotherapy , Actuarial Analysis , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carmustine/administration & dosage , Central Nervous System Diseases/etiology , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/mortality , Combined Modality Therapy , Cranial Irradiation/adverse effects , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Lymphoma/drug therapy , Lymphoma/mortality , Male , Methotrexate/administration & dosage , Middle Aged , Radiotherapy Dosage , Spain/epidemiology , Survival Rate , United Kingdom/epidemiology , Vincristine/administration & dosage
15.
Clin Oncol (R Coll Radiol) ; 13(4): 269-72, 2001.
Article in English | MEDLINE | ID: mdl-11554623

ABSTRACT

In the 10-year period 1987 to 1996, 24 patients were diagnosed with aggressive non-Hodgkin's lymphoma of the nasal cavities or paranasal sinuses. The disease occurred in a relatively elderly population of median age 72 years (range 42 to 96) with a male predominance (male 15; female nine). The histology on review was mostly of the large B-cell subtype (21 patients); peripheral T-cell subtype (one), anaplastic large cell of T-cell type (one) and T/natural killer cell nasal lymphoma (one). The disease was localized in 20 patients (Stage IEA). The overall survival at 5 years was 40% (95% confidence interval (CI) 19-61); at 10 years it was 33% (95% CI 12-54). The cause-specific survival (excluding deaths from causes other than lymphoma) at 5 years and 10 years was 62% (95% CI 39-86).


Subject(s)
Lymphoma, Non-Hodgkin/therapy , Nasal Cavity , Nose Neoplasms/therapy , Paranasal Sinus Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/mortality , Lymphoma, B-Cell/therapy , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/mortality , Lymphoma, T-Cell/diagnosis , Lymphoma, T-Cell/mortality , Lymphoma, T-Cell/therapy , Male , Middle Aged , Neoplasm Invasiveness , Nose Neoplasms/diagnosis , Nose Neoplasms/mortality , Paranasal Sinus Neoplasms/diagnosis , Paranasal Sinus Neoplasms/mortality , Survival Rate
16.
Br J Cancer ; 84(10): 1293-300, 2001 May 18.
Article in English | MEDLINE | ID: mdl-11355937

ABSTRACT

The purpose of this randomized trial was to compare the efficacy of 6 cycles of prednisolone, Adriamycin (doxorubicin), bleomycin, vincristine (Oncovin) and etoposide (PABlOE) with 3 cycles of PABIOE that alternate with 3 cycles of chlorambucil, vinblastine, procarbazine and prednisone (ChlVPP) in patients with advanced Hodgkin's disease. Between October 1992 and April 1996, 679 patients were entered onto the study. 41 of these did not match the protocol requirements on review and were excluded from further analysis, most of these being reclassified as NHL on histological review. Of the remaining 638 patients, 319 were allocated to receive PABIOE and 319 were allocated to receive ChlVPP/PABlOE. The complete remission (CR) rates were 78% and 64%, for ChlVPP/PABlOE and PABIOE respectively after initial chemotherapy (P< 0.0001). 124 patients were re-evaluated subsequently following radiotherapy to residual masses. The CR rates changed from 78% to 88% for ChlVPP/PABlOE and from 64% to 77% for PABlOE when re-evaluated in this manner (treatment difference still significant, P = 0.0002). The treatment associated mortality in the PABlOE arm was 2.2% (7 deaths), while there were no such deaths in the ChlVPP/PABlOE arm (P = 0.015). The failure-free survival was significantly greater in the ChlVPP/PABlOE arm (P< 0.0001) as was the overall survival (P = 0.01). The failure-free and overall survival rates at 3 years were 77% and 91% in the ChlVPP/PABlOE arm, compared with 58% and 85% in the PABIOE arm, respectively. These results indicate that ChlVPP alternating with PABIOE is superior to PABIOE alone as initial treatment for advanced Hodgkin's disease.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hodgkin Disease/drug therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bleomycin/administration & dosage , Bleomycin/adverse effects , Chlorambucil/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Hodgkin Disease/mortality , Hodgkin Disease/pathology , Humans , Male , Middle Aged , Neoplasm Staging , Prednisolone/administration & dosage , Prednisolone/adverse effects , Prednisone/administration & dosage , Procarbazine/administration & dosage , Survival Rate , Vinblastine/administration & dosage , Vincristine/administration & dosage , Vincristine/adverse effects
17.
Int J Radiat Oncol Biol Phys ; 50(2): 457-64, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11380234

ABSTRACT

PURPOSE: To assess the efficacy and toxicity, including long-term neurotoxicity, of combined therapy with the CHOD/BVAM regimen given before cranial radiotherapy in the treatment of primary CNS lymphoma (PCNSL). METHODS AND MATERIALS: Thirty-one consecutive patients with PCNSL were treated with one cycle of cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD) and two of carmustine (BCNU), vincristine, cytosine arabinoside, and methotrexate (BVAM), followed by cranial radiotherapy (45 Gy whole brain plus a 10-Gy boost for single lesions). The median age was 59 years (range 21-70) and 39% had poor performance status. The median follow-up of patients was 4.1 years (range 2.7-9.0). RESULTS: Twenty-one patients had no PCNSL at the end of treatment. The 5-year actuarial probability of survival was 31% (95% confidence interval [CI]: 11%-57%), with a median survival of 38 months. Patients < 60 years had a survival significantly longer than those > or = 60 years (4-year survival: 58% (95% CI: 34-82%) vs. 29% (95% CI: 5-53%), respectively; p = 0.04). Two patients died during chemotherapy from pulmonary embolism and bronchopneumonia, respectively, with no evidence of PCNSL at the autopsy. Dementia probably related to treatment occurred in 5 (62%) of the 8 patients 60 years and older, and 4 of them died without evidence of relapse of PCNSL. Dementia correlated with developing brain atrophy and leuco-encephalopathy on serial CT or MR scans. CONCLUSION: This regimen can be given with the planned dose intensity to patients aged less than 70 years, and produces better survival than that reported with radiotherapy alone; however, dementia occurs in the majority of patients aged 60 years of age or more.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/radiotherapy , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carmustine/administration & dosage , Carmustine/adverse effects , Combined Modality Therapy , Cranial Irradiation , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Cytarabine/administration & dosage , Cytarabine/adverse effects , Dexamethasone/administration & dosage , Dexamethasone/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Female , Humans , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Survival Rate , Vincristine/administration & dosage , Vincristine/adverse effects
18.
Br J Neurosurg ; 14(4): 313-5; discussion 316, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11045195

ABSTRACT

The prognosis for primary cerebral non-Hodgkin's lymphoma has improved markedly in the under-70 age group with the introduction of combined chemotherapy and radiotherapy. A review of our patients has revealed difficulty in obtaining definitive histology initially in 21% (9/43). We investigated the role of corticosteroids in these patients and found an idiosyncratic response in that there was no significance either of the cumulative dose (p > 0.424) or the length of treatment (p > 0.453) with the observed regression of lymphoma with corticosteroids. In order to avoid indiscriminate corticosteroid administration we have formulated a management protocol the entry point for which is a patient with enhanced computered tomography appearances of primary cerebral lymphoma.


Subject(s)
Brain Neoplasms/diagnosis , Lymphoma, Non-Hodgkin/diagnosis , Adult , Age Distribution , Aged , Aged, 80 and over , Anti-Inflammatory Agents/therapeutic use , Brain Neoplasms/drug therapy , Clinical Protocols , Dexamethasone/therapeutic use , Female , Humans , Lymphoma, Non-Hodgkin/drug therapy , Male , Middle Aged , Prospective Studies , Retrospective Studies
19.
Laryngoscope ; 110(9): 1489-92, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10983948

ABSTRACT

OBJECTIVES: A review of the presenting features, management, and outcome of extranodal non-Hodgkin's lymphoma (NHL) of the sinonasal tract during a 10-year period in Nottingham, UK. STUDY DESIGN: Twenty-four patients received a diagnosis of extranodal NHL of the nasal cavity, paranasal sinuses, or both, from 1987 to 1996. The patients' data were collected prospectively in the Nottinghamshire Lymphoma Registry. METHODS: All patients' records and their histology were reviewed along with data entered into the Nottinghamshire Lymphoma Registry, noting the patient's age, sex, presenting symptoms and signs, staging, computed tomography findings, histology, treatment, complications, and outcome. RESULTS: The 24 patients with extranodal NHL of the sinonasal tract represent 1.63% of the 1,457 patients with NHL seen in the 10-year period of this study in Nottinghamshire. The median age was 72 years (range, 42-96 y), with a male dominance (male-to-female ratio: 15:9). Most patients presented with nonspecific nasal symptoms such as nasal obstruction and epistaxis. Only one patient had a relapse involving the central nervous system after treatment. All the histology was reviewed and showed a predominance of large B-cell subtype (21 patients). The overall 5-year survival was 40% (95% CI, 19%-61%) and 33% for 10-year (95% CI, 12%-54%). The cause-specific survival at 5 years and 10 years was 62% (95% CI, 39%-86%). CONCLUSIONS: A high degree of suspicion and appropriate use of computed tomography scans and surgical biopsy are the keys to the management of NHL.


Subject(s)
Lymphoma, Non-Hodgkin , Paranasal Sinus Neoplasms , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Lymphoma, Non-Hodgkin/diagnosis , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Neoplasm Staging , Paranasal Sinus Neoplasms/diagnosis , Paranasal Sinus Neoplasms/mortality , Paranasal Sinus Neoplasms/therapy , Prospective Studies , Registries , Survival Rate , Tomography, X-Ray Computed , United Kingdom/epidemiology
20.
Br J Haematol ; 109(1): 81-8, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10848785

ABSTRACT

Follicular lymphoma (FL) cells express CD20 and are associated in most cases with the t(14;18) chromosomal translocation. A multicentre study was undertaken between January 1997 and January 1998 to assess the complete response rate (CR) and overall response rate (RR) to rituximab, a chimaeric anti-CD20 monoclonal antibody. Seventy patients with previously treated FL received rituximab (375 mg/m2/week x4, by intravenous infusion). Restaging studies were performed 1 and 2 months after therapy. Molecular monitoring for the presence of cells harbouring the Bcl-2/JH gene rearrangement in the peripheral blood (PB) and bone marrow (BM) was performed before and after treatment using a two-step semi-nested polymerase chain reaction (PCR) assay. The overall RR was 32/70 (46%), being highest in patients who had received only one previous treatment (12/15, 80%). However, only two patients achieved a CR. The median duration of response was 11 months. Thirteen of 21 evaluable 'PCR-positive' patients (62%) became 'PCR-negative' in PB and/or BM samples 1 month after rituximab, although this did not correlate with clinical response. Treatment was generally well tolerated, although one patient developed Stevens-Johnson syndrome. Rituximab was shown to be active in FL, and in some cases PB and/or BM became PCR negative. Studies in combination with cytotoxic chemotherapy to increase the CR rate are warranted.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antigens, CD20/immunology , Lymphoma, Follicular/drug therapy , Adult , Aged , Animals , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Murine-Derived , Female , Follow-Up Studies , Gene Rearrangement , Genes, bcl-2 , Humans , Lymphoma, Follicular/genetics , Male , Mice , Middle Aged , Polymerase Chain Reaction , Recombinant Fusion Proteins/therapeutic use , Rituximab , Treatment Outcome
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