Biomedical subjects

Roger A'Hern

Publications and source records attributed to Roger A'Hern.

At least 19 recordsLinked to original sources

PubMed2007

Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer.

Tumor expression of the proliferation antigen Ki67 is widely used to assess the prognosis of cancer patients. A change in the expression of Ki67 after short-term exposure of patients to therapeutic agents is frequently used as a pharmacodynamic marker of efficacy, particularly among breast cancer patients before undergoing surgery. To determine the clinical significance of the level of tumor cell proliferation during endocrine therapy for breast cancer, we measured the expression of Ki67 in tumor biopsy samples taken before and after 2 weeks of presurgical treatment with anastrozole or tamoxifen or the combination of anastrozole plus tamoxifen in 158 patients with hormone receptor-positive primary disease. In a multivariable analysis, we found that higher Ki67 expression after 2 weeks of endocrine therapy was statistically significantly associated with lower recurrence-free survival (P = .004) whereas higher Ki67 expression at baseline was not. Larger baseline tumor size and lower estrogen receptor level after 2 weeks of treatment were also statistically significantly associated with poorer recurrence-free survival (P < .001 and P = .04, respectively). Our data indicate that measurements of tumor Ki67 level after short-term endocrine treatment may improve the prediction of recurrence-free survival by integrating the prognostic value of Ki67 level at baseline with changes in Ki67 level that are associated with treatment benefit.

Adult↗

PubMed2006

Manually after-loaded 192Ir low-dose rate brachytherapy after subtotal excision and flap reconstruction of recurrent cervical lymphadenopathy from head and neck cancer.

BACKGROUND: Treatment of extensive recurrent cervical lymph node metastases from previously irradiated head and neck cancer represents a difficult clinical challenge. We report the results of an approach of maximal surgical debulking and manually after-loaded intra-operative brachytherapy. PATIENTS AND METHODS: Seventy-four procedures were carried out at the Royal Marsden Hospital between 1979 and 2003. All patients had previously been treated with radical radiotherapy or chemoradiation. Patients underwent maximal surgical debulking, followed by brachytherapy to the tumour bed with low-dose rate (192)Ir to a dose of 60 Gy to the reference isodose using the Paris system. RESULTS: Overall and disease specific survival rates were 31% and 28% at two years and 23% and 17% at five years. Corresponding Loco-regional control rates were 37% and 23%, respectively. Fifty per cent of patients developed metastatic disease within 5 years of treatment. Best results were obtained with surgical excision, brachytherapy and reconstruction of the skin defect using a vascularised myo-cutaneous flap with in-field control rates of 72% at two years and 66% at 5 years. Nine per cent of patients developed fistulae, 4% had haemorrhage and 8% wound breakdown/infection. CONCLUSIONS: Maximal surgical debulking, including removal of overlying skin, and brachytherapy to the surgical tumour bed provides high levels of local control, and can be achieved with acceptable morbidity. Only a minority of patients achieve long-term survival because of the high risk of systemic relapse.

Adult↗

PubMed2006

Randomized phase II study comparing thalidomide with medroxyprogesterone acetate in patients with metastatic renal cell carcinoma.

PURPOSE: To investigate escalating doses of thalidomide compared with medroxyprogesterone in patients with metastatic renal cell carcinoma (RCC), who had either progressed after first-line immunotherapy or who were not suitable for immunotherapy. PATIENTS AND METHODS: Thalidomide was started at 100 mg/d orally (PO) and escalated by 100 mg/d every 2 weeks to the maximum dose of 400 mg/d. Medroxyprogesterone was given at a fixed dose of 300 mg PO daily. RESULTS: Sixty patients were entered (thalidomide:medroxyprogesterone = 29:31; median age, 59 [thalidomide], 60 [medroxyprogesterone]; No. of patients assessable for response, 22 [thalidomide], 26 [medroxyprogesterone]). In the thalidomide arm, there was no objective response seen. The best response was SD in three patients lasting 5+, 6+, and 12 months, respectively. All patients in the medroxyprogesterone arm progressed. There was no difference in overall survival between the two arms; median survival in the thalidomide arm was 8.2 months compared with 4.8 months in the medroxyprogesterone arm (P = .62). Hazard ratio was 0.88 (95% CI, 0.67 to 1.94). Median duration of treatment was 73 days (range, 14 to 364 days) in the thalidomide arm, and 84 days (range, 7 to 175 days) in the medroxyprogesterone arm. The high incidence of toxicity in the thalidomide arm, mainly somnolence, constipation, fatigue and paraesthesia, meant that only 30.8% of patients were able to tolerate the maximum dose of 400 mg/d of treatment. CONCLUSION: Thalidomide is not superior to medroxyprogesterone acetate in patients with metastatic RCC. Its risk/benefit ratio does not favor its use in this patient population.

Adult↗

PubMed2006

Proliferation and apoptosis as markers of benefit in neoadjuvant endocrine therapy of breast cancer.

The study of changes in proliferation as a marker of treatment benefit during presurgical endocrine treatment of breast cancer has become increasingly popular, particularly using the nuclear marker Ki67, and holds the potential for prioritizing new treatments for full clinical development. There are weakly significant relationships between Ki67 change and clinical response that differ according to data handling. In the neoadjuvant Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen trial, suppression of Ki67 at both 2 and 12 weeks was greater with the aromatase inhibitor anastrozole than with either tamoxifen or the combination of anastrozole and tamoxifen. We report here that absolute values of Ki67 after 2 weeks were also significantly lower with anastrozole than with tamoxifen and the combination. This indicates that it may be possible to make such comparisons using surgical samples only. We argue that these changes in proliferation and concurrent changes in apoptosis may be expected to be more predictive of adjuvant benefit from endocrine therapy than clinical response.

Anastrozole↗

PubMed2005

The impact of introducing intensity modulated radiotherapy into routine clinical practice.

BACKGROUND AND PURPOSE: Intensity modulated radiotherapy (IMRT) at the Royal Marsden Hospital London was introduced in July 2001. Treatment delivery was dynamic using a single-phase technique. Concerns were raised regarding increased clinical workload due to introduction of new technology. The potential increased use of resources was assessed. PATIENTS AND METHODS: IMRT patient selection was within guidelines of clinical trials and included patients undergoing prostate plus pelvic lymph node (PPN) irradiation and head and neck cancer (HNC) treatment. Patient planning, quality assurance and treatment times were collected for an initial IMRT patient group. A comparative group of patients with advanced HNC undergoing two- or three-phase conventional radiotherapy, requiring matched photon and electron fields, were also timed. RESULTS: The median overall total planning time for IMRT was greater for HNC patients compared to the PPN cohort. For HNC the overall IMRT planning time was significantly longer than for conventional. The median treatment time for conventional two- or three-phase HNC treatments, encompassing similar volumes to those treated with IMRT, was greater than that for the IMRT HNC patient cohort. A reduction in radiographer man hours per patient of 4.8h was recorded whereas physics time was increased by 4.9h per patient. CONCLUSIONS: IMRT currently increases overall planning time. Additional clinician input is required for target volume localisation. Physics time is increased, a significant component of this being patient specific QA. Radiographer time is decreased. For HNC a single phase IMRT treatment has proven to be more efficient than a multiple phase conventional treatment. IMRT has been integrated smoothly and efficiently into the existing treatment working day. This preliminary study suggests that IMRT could be a routine treatment with efficient use of current radiotherapy resources.

Cohort Studies↗

PubMed2005

Zeta-chain associated protein 70 and CD38 combined predict the time to first treatment in patients with chronic lymphocytic leukemia.

BACKGROUND: Zeta-chain associated protein (ZAP)-70 has been proposed as a surrogate marker for immunoglobulin heavy-chain variable region (IgVH) mutation in chronic lymphocytic leukemia (CLL), but it is still not clear whether it is an independent prognostic factor. METHODS: The authors evaluated ZAP-70 expression by flow cytometry in 201 untreated patients and correlated ZAP-70 levels with CD38 expression, genetic abnormalities detected by fluorescence in situ hybridization (FISH), and the time from diagnosis to first treatment. RESULTS: Fifty-seven patients (28%) were positive for ZAP-70 (> or = 20%). Positive ZAP-70 status was associated with advanced disease stage, atypical morphology, CD38-positive status, trisomy 12, del(6q), or no detectable abnormalities; negative ZAP-70 status was correlated with del(13q) as a sole abnormality. The treatment-free interval (TFI) was 17.7 months for ZAP-70-positive patients and 44.6 months for ZAP-70-negative patients (P < 0.001). Multivariate analysis in 117 patients identified advanced stage, CD38 > or = 7%, and the absence of del(13q) as a sole abnormality as independent factors for short TFI. Excluding FISH, ZAP-70 status acquired independent prognostic value along with CD38 status. The authors proposed a risk model that combines ZAP-70 and CD38 to identify patients who are likely to progress. When both markers were positive, the TFI was 12 months; when both were negative, the median TFI was 54 months; a median TFI of 26 months was observed in patients who had discordant results (P < 0.00001). CONCLUSIONS: The current findings suggested that both ZAP-70 and CD38 should be tested prospectively in all patients with early-stage CLL.

ADP-ribosyl Cyclase 1↗

PubMed2005

Evaluation of outcome after immediate breast reconstruction: prospective comparison of four methods.

BACKGROUND: Little is known about the association among different methods to assess outcome following breast reconstruction. The aim of this study was to comprehensively compare four distinct methods of outcome evaluation following immediate breast reconstruction. METHODS: There were 102 women who were prospectively evaluated: 46 patients had submuscular implants, and 56 patients had implant-assisted latissimus dorsi breast reconstruction. The mean patient age at the time of operation was 46 years (range, 22 to 72 years), with a mean follow-up of 18 months (range, 12 to 24 months). All patients were evaluated using geometric measurements, photographs, linear analogue scores, and a quality-of-life questionnaire. The Wilcoxon signed rank test, Spearman's correlation, and factor analysis statistics were used. RESULTS: Transverse breast width, vertical breast height, sternal notch-nipple, midclavicular line-nipple, nipple-inframammary crease, midline-nipple, internipple, and intermammary measurements were reproducible and reliable. Median differences of absolute vertical and horizontal differences were less than 1 cm and were associated with high levels of patient satisfaction. Assessors asked to score photographs without being specifically requested to consider shape, cleavage, or symmetry would focus mainly on vertical and horizontal differences. There was a high correlation between surgeon and patient linear analogue scores. Quality-of-life questionnaires provide valuable information on body image, physical effects, and continued cancer worry. Factor analyses failed to identify components to compress data fields to obtain equivalent information from fewer questions. CONCLUSIONS: Evaluation of immediate breast reconstruction is complex. Cumbersome data collection has to be balanced against practical variables that individual units can collect to evaluate outcome for audit and research.

Adult↗

PubMed2005

Surgical excision of isolated renal-bed recurrence after radical nephrectomy for renal cell carcinoma.

OBJECTIVE: To present our results on managing loco-regional recurrence of renal cell carcinoma (RCC) with surgical excision, as local recurrence at the site of a previous nephrectomy is resistant to both systemic therapy and radiotherapy. PATIENTS AND METHODS: In all, 16 patients were operated on between 1994 and 2003 for local recurrence of RCC. The median (mean, range) age at the time of local recurrence was 57.9 (57.4, 28.9-71.7) years, and the median interval from primary surgery 2.22 (3.88, 0.27-14.46) years. Before surgery eight patients had been given systemic immunotherapy, with no response of their local recurrence. RESULTS: Two patients were deemed inoperable because of direct invasion of the great vessels and the liver by tumour. The remaining 14 patients had recurrence in residual adrenal tissue (two), para-aortic nodes (three), para-caval nodes (two), retrocaval nodes (one), renal bed (six), liver, spleen and stomach (one each), and diaphragm (two). Although complete macroscopic en-bloc clearance was achieved in these patients, only eight had tumour-free margins on histological examination. The histology was consistent with RCC recurrence in all cases. All of the patients were followed with computed tomography at regular intervals. At a median follow-up of 1.0 (1.65, 0.25-6.5) years, five patients remain disease-free, four have local and distant relapse, and five developed distant metastasis only. The presence of tumour at the resection margin was a significant factor in predicting local and distant disease-free survival (P < 0.05). CONCLUSIONS: En bloc excision of isolated locally recurrent RCC is possible, and complete surgical extirpation can lead to prolonged disease-free survival.

Adult↗

PubMed2004

Primary malignant tumors of the iliopsoas compartment.

BACKGROUND AND OBJECTIVES: Primary malignant tumors of the iliopsoas compartment are rare entities that have been infrequently reported. We present our experience of iliopsoas malignancy to better characterize and define the natural history of this condition. METHODS: Primary iliopsoas tumors occurring from January 1990 were identified from the Royal Marsden Hospital's (RMH) Sarcoma Unit prospective database. RESULTS: Nineteen malignant tumors (11 limited to the psoas muscle only, 1 involving only the iliacus muscle and 7 involving both the iliacus and psoas) of the iliopsoas compartment were evaluated and treated at the RMH during this period. Leiomyosarcoma (n = 5) and liposarcoma (n = 3) were the most frequent histologic types. There were 3 G1, 5 G2, 10 G3 tumors and grade could not be assessed in 1 patient. There were 17 T2 tumors and size was not available in 2 patients. Surgery was done in 14 patients (negative microscopic margins-7, positive microscopic margins-3, and positive gross margins-3 and the margin of excision was not known in 1 patient). Five of 14 surgically treated patients had local recurrence and 6 of 19 patients developed metastases. Ten patients died of their disease at a median follow-up of 12 months. The estimated 2 and 5 year survival rates were 44 and 23%, respectively. CONCLUSIONS: Tumors in this location have a poor prognosis due to the lack of early diagnosis, large size at presentation, multiple attachments of the psoas muscle, and being relatively surgically inaccessible.

Chemotherapy, Adjuvant↗

PubMed2004

Mucinous epithelial ovarian cancer: a separate entity requiring specific treatment.

PURPOSE: Invasive mucinous carcinoma of the ovary (mucinous epithelial ovarian cancer [mEOC]) is a histologic subgroup of epithelial ovarian cancer (EOC). Chemotherapy for mEOC is chosen according to guidelines established for EOC. The purpose of this study is to determine whether this is appropriate. PATIENTS AND METHODS: Women with advanced mEOC (International Federation of Gynecology and Obstetrics stage III or IV) who underwent first-line platinum-based chemotherapy were compared with women with other histologic subtypes of EOC in a case-controlled study. RESULTS: Eighty-one patients (27 cases, 54 controls) treated with platinum-based regimens were analyzed. The response rates for cases and controls were 26.3% (95% CI, 9.2% to 51.2%) and 64.9% (95% CI, 47.5% to 79.8%), respectively (P=.01). The odds ratio for complete or partial response to chemotherapy for mEOC was 0.19 (95% CI, 0.06 to 0.66; P=.009) compared with other histologic subtypes of EOC. Median progression-free survival was 5.7 months (95% CI, 1.9 to 9.6 months) versus 14.1 months (95% CI, 12.0 to 16.2 months; P<.001) and overall survival was 12.0 months (95% CI, 8.0 to 15.6 months) versus 36.7 months (95% CI, 25.2 to 48.2 months; P<.001) for cases and controls, respectively. The hazard ratio for progression and death was 2.94 (95% CI, 1.71 to 5.07; P<.001) and 3.08 (95% CI, 1.69 to 5.6; P<.001), respectively, for mEOC patients as compared with controls. CONCLUSION: Patients with advanced mEOC have a poorer response to platinum-based first-line chemotherapy compared with patients with other histologic subtypes of EOC, and their survival is worse. Specific alternative therapeutic approaches should be sought for this group of patients, perhaps involving fluorouracil-based chemotherapy.

Adenocarcinoma, Mucinous↗

PubMed2004

Excision margins in high-risk malignant melanoma.

BACKGROUND: Controversy exists concerning the necessary margin of excision for cutaneous melanoma 2 mm or greater in thickness. METHODS: We conducted a randomized clinical trial comparing 1-cm and 3-cm margins. RESULTS: Of the 900 patients who were enrolled, 453 were randomly assigned to undergo surgery with a 1-cm margin of excision and 447 with a 3-cm margin of excision; the median follow-up was 60 months. A 1-cm margin of excision was associated with a significantly increased risk of locoregional recurrence. There were 168 locoregional recurrences (as first events) in the group with 1-cm margins of excision, as compared with 142 in the group with 3-cm margins (hazard ratio, 1.26; 95 percent confidence interval, 1.00 to 1.59; P=0.05). There were 128 deaths attributable to melanoma in the group with 1-cm margins, as compared with 105 in the group with 3-cm margins (hazard ratio, 1.24; 95 percent confidence interval, 0.96 to 1.61; P=0.1); overall survival was similar in the two groups (hazard ratio for death, 1.07; 95 percent confidence interval, 0.85 to 1.36; P=0.6). CONCLUSIONS: A 1-cm margin of excision for melanoma with a poor prognosis (as defined by a tumor thickness of at least 2 mm) is associated with a significantly greater risk of regional recurrence than is a 3-cm margin, but with a similar overall survival rate.

Adolescent↗

PubMed2004

Characterisation of TP53 abnormalities in chronic lymphocytic leukaemia.

Abnormalities of TP53 in chronic lymphocytic leukaemia (CLL) correlate with aggressive disease and transformation. We studied 115 patients with CLL including 90 untreated, 25 with heavily pretreated/refractory CLL using fluorescent in situ hybridisation (FISH) to detect allelic loss at chromosome 17p and flow cytometry (FC) to test p53 protein overexpression. A total of 17 cases were identified with TP53 deletion and/or protein expression. Both tests correlated in 10 of 17 patients; in six, one or the other abnormality was detected and in one case, with a deletion, flow cytometry failed. Material for direct DNA sequencing was available in 14 of 17 cases. Mutations were found in seven cases. Five of 14 patients with allelic loss and seven of 13 expressing p53 protein had a mutation. These were single-base substitutions and were located in exons 5, 7 or 8. Mutations were not found in 13 of 14 other cases without deletions by FISH or protein expression. The incidence of p53 abnormalities in this series was 15%, with a significant difference between untreated patients (7%) and the pretreated/refractory group (50%; P<0.01). Abnormal p53 was predicted for shorter survival, regardless of the method used. We confirm that p53 abnormalities are more common in refractory CLL and that mutations occur at the known hot spots. Testing for TP53 deletions by FISH and protein expression by FC is an effective and simple way of screening patients who are likely to have aggressive disease. DNA sequencing adds little to these methods in identifying the population at risk.

DNA Mutational Analysis↗

PubMed2004

Prognosis of lymph node metastasis in soft tissue sarcoma.

BACKGROUND: We defined the tumor characteristics and prognosis of patients with regional lymph node metastasis (RLNM) from soft tissue sarcoma. METHODS: All patients with RLNM from soft tissue sarcoma were identified from the Royal Marsden Hospital Sarcoma Unit prospective database from January 1990. RESULTS: A total of 73 (3.4%) of 2127 patients had RLNM. Fifty-seven patients (78.1%) had RLNM as the first site of spread, and 16 patients (21.9%) presented with RLNM and distant metastasis synchronously. The most common histologies were rhabdomyosarcoma, epithelioid sarcoma, and angiosarcoma. There were 9 T1 and 36 T2 tumors, and tumor size was not available in 28 patients. There were 6 grade 1, 16 grade 2, and 51 grade 3 tumors. Forty-two patients presented with RLNM along with the primary tumor. Of the remaining patients, the median time to development of RLNM from diagnosis of the primary tumor was 13.5 months (95% confidence interval [CI], 1-100 months). The 1-year survival for patients with isolated RLNM was 77.49% (95% CI, 62.99%-86.88%), compared with 36.27% (95% CI, 13.32%-60.04%) for patients who presented with RLNM and distant metastasis (P =.005). The 1-year survival for metachronous and synchronous RLNM was 94.44% (95% CI, 66.64%-99.20%) and 67.54% (95% CI, 47.89%-81.12%), respectively (P =.05). CONCLUSIONS: Lymph node metastasis is rare. Patients who present with isolated RLNM have an improved survival compared with patients who present with regional and distant metastasis at diagnosis. Synchronous RLNM with the primary tumor have a poorer outcome than metachronous RLNM in the absence of distant metastasis.

Adolescent↗

PubMed2004

The diagnostic value of CD123 in B-cell disorders with hairy or villous lymphocytes.

BACKGROUND AND OBJECTIVES: CD123 is an antibody that identifies the a chain of the human interleukin-3 receptor and is expressed in a variety of normal hematopoietic cells, acute leukemia and hairy cell leukemia (HCL). The aim of the study was to investigate the diagnostic value of CD123 expression in B-cell disorders with circulating hairy and villous lymphocytes. DESIGN AND METHODS: We investigated the diagnostic value of CD123 expression in neoplastic cells from 59 patients with B-cell disorders with circulating hairy or villous lymphocytes: HCL (n=24), the variant form of HCL (n=11) and splenic lymphoma with villous lymphocytes (SLVL) (n=24). Cells from 12 patients with chronic lymphocytic leukemia were used as controls. Immunophenotypic analysis was performed by flow cytometry on 77 samples from peripheral blood (n=48), bone marrow (n=25) and spleen cell suspensions (n=4). RESULTS: Our findings show that cells from 95% of typical HCL express CD123 with strong to moderate intensity while this molecule is absent in circulating cells from most cases of HCL-variant (91%) and SLVL (97%). INTERPRETATION AND CONCLUSIONS: We conclude that CD123 is a useful new marker for distinguishing B-cell disorders with circulating villous lymphocytes as its expression is characteristic of typical HCL with high sensitivity and specificity. However CD123 does not allow the distinction between HCL-variant and SLVL, as both are CD123 negative.

Antibodies, Monoclonal↗

PubMed2003

Comparison of the selective estrogen receptor modulator arzoxifene (LY353381) with tamoxifen on tumor growth and biomarker expression in an MCF-7 human breast cancer xenograft model.

Arzoxifene (ARZ) is a selective estrogen receptor (ER) modulator with greater bioavailability than raloxifene which is being developed as treatment for breast cancer. We have used an in vivo model of hormone-sensitive breast cancer to study the growth-inhibitory and pharmacodynamic effects of ARZ in comparison with the most widely used antiestrogen, tamoxifen (TAM). We compared the abilities of ARZ and TAM to antagonize the estrogen (E2)-dependent growth of MCF-7 human breast cancer xenografts in oophorectomized athymic mice. At four different time points over 28 days, we studied their time-related pharmacodynamic effects on biomarkers of tumor growth (cell proliferation/death measured by Ki-67 and apoptosis scores), cell cycle activity (cyclin D1 and p27(kip1)), and hormone-regulated gene expression (ERalpha, progesterone receptor, and pS2). Although maximal growth inhibition was seen after E2 withdrawal, ARZ and TAM induced significant and similar inhibition of E2-stimulated tumor growth. Inhibition of growth was reflected by changes in the tumor growth index (ratio posttreatment/pretreatment Ki-67/apoptosis scores). ARZ and TAM resulted in a significant (P < 0.001) increase in ER expression and reduction in progesterone receptor expression, whereas changes in cyclin D1 score were inversely related to p27(kip1) score. A significant but delayed biological effect was observed with a 10-fold lower dose of ARZ. These results show that ARZ is an effective antagonist of E2-stimulated breast cancer growth with similar growth-inhibitory and pharmacodynamic effects to TAM in this model.

Animals↗

PubMed2003

Can patients with relapsed, previously untreated, stage I epithelial ovarian cancer be successfully treated with salvage therapy?

PURPOSE: The role of adjuvant chemotherapy in early-stage epithelial ovarian cancer (EOC) has been controversial. We have previously reported the cases of patients managed with a policy of observation only. We now present the salvage rate for the patients in that study who experienced relapse. PATIENTS AND METHODS: One hundred ninety-four patients with stage I EOC presenting between 1980 and 1994 received no adjuvant chemotherapy, but were treated with platinum-based chemotherapy at relapse. We calculated the progression-free survival (PFS) and overall survival (OS) for the whole cohort and the salvage rate for those who experienced relapse. We defined salvage as freedom from relapse for 5 years after platinum treatment. RESULTS: Sixty-one (31%) of 194 patients experienced relapse, and 55 received platinum-based chemotherapy. Twenty-four percent were progression-free at 5 years after this treatment. Clear-cell histology and cyst rupture before the patients' original surgery were independent prognostic factors for PFS after salvage chemotherapy. The OS for all 194 patients is 72% at 10 years (median follow-up, 8.7 years), with an 80% disease-specific survival (DSS). CONCLUSION: We have shown that some patients with stage I EOC can be successfully treated with a salvage chemotherapy regimen after a policy of observation only. Interestingly, approximately 30% of stage I patients who die within 10 years do so from causes other than EOC (OS, 72%; DSS, 80%). Our findings need to be taken into consideration when the results from recent randomized trials of adjuvant chemotherapy in this patient population (International Collaborative Ovarian Neoplasm Trial 1/European Organization for Research and Treatment of Cancer Adjuvant Chemotherapy in Ovarian Neoplasm Trial) are being discussed with patients.

Adult↗

PubMed2003

Long-term results in elderly patients with differentiated thyroid carcinoma.

BACKGROUND: The authors assessed the biologic behavior of differentiated thyroid carcinoma in patients age 70 years or older and evaluated factors that influenced long-term survival. METHODS: Among 1448 patients with differentiated thyroid carcinoma who were treated at the authors' institution over the past 60 years, 111 patients were identified who were age 70 years or older at the time of their initial diagnosis (range, 70-93 years). The authors conducted a retrospective analysis of the outcome of these 111 patients, who had a median follow-up of 9 years (range, 2-9 years). RESULTS: There were 83 female patients and 28 male patients (female to male ratio, 3:1). Fifty-eight tumors were papillary, 46 tumors were follicular, and 7 tumors were Hürthle cell carcinoma. Eighty percent of patients presented with a thyroid mass, and 70% of tumors were pathologic stage T3 (pT3) or pT4. Lymph node disease was evident at presentation in 44% of patients, and distant metastases were documented at diagnosis in 23% of patients. Forty-six patients underwent total thyroidectomy, and the remaining patients underwent subtotal thyroidectomy or biopsy only. Radioiodine was administered to 80 patients, and external beam radiotherapy was administered to 19 patients. The cause specific survival rates were 75%, 50%, and 50% at 5 years, 10 years, and 15 years, respectively. Multivariate analysis showed that the presence of metastases was the most important independent prognostic factor for survival. External beam radiotherapy was associated with a poorer prognosis, in that it was reserved for patients with either inoperable disease or residual disease after surgery and patients with no uptake of radioiodine. CONCLUSIONS: A large proportion of thyroid tumors showed extrathyroid spread and distant metastases, which frequently were not iodine-avid. The prevalent histologic type was papillary, often with features of poor differentiation. Thyroid carcinoma in the elderly appears to behave more aggressively, and they have a less favorable prognosis compared with younger adults.

Age Factors↗

PubMed2003

Le Fort I osteotomy and low-dose rate Ir192 brachytherapy for treatment of recurrent nasopharyngeal tumours.

BACKGROUND: Treatment of recurrent nasopharyngeal carcinoma is a difficult clinical problem. External beam re-irradiation is associated with a long-term cure in a proportion of cases but this may be associated with severe radiation injury. METHODS: Eighteen patients with post-nasal space tumours were treated between 1986 and 2001 with surgical excision and nasopharyngeal brachytherapy via a Le Fort I osteotomy approach. Low-dose rate (LDR) and high-dose rate (HDR) brachytherapy was used. Data was prospectively collected. Local control and overall survival were measured. Acute and late complications were assessed using the RTOG system. RESULTS: The overall survival was 67% at 2 years and 33.5% at 5 years. The corresponding local control rates were 42 and 31.5%, respectively. The T stage at relapse was a significant prognostic factor for local control (P=0.004) but not overall survival. Acute toxicity was mild. RTOG grade >/=3 late complications occurred in 40% of patients treated with the HDR, and 0% treated with LDR. CONCLUSIONS: The results of the Le Fort osteotomy, tumour debulking and post-operative brachytherapy gives local control rates similar to those achieved with wide-field re-irradiation. Complication rates are acceptable and are lower than that reported with other methods of radiation therapy. The surgical technique was well tolerated. HDR brachytherapy with this technique had a high complication rate. This approach is a viable option in the treatment of recurrent nasopharyngeal tumours.

Adult↗