ABSTRACT
AIMS: Management of the clinically node-negative (cN0) neck for parotid tumours remains controversial. Options include observation, elective neck dissection (END) or elective nodal irradiation (ENI). We reviewed the evidence for ENI on a background of current practice among UK clinical oncologists. MATERIALS AND METHODS: We carried out a systematic search of PubMed between 1 January 1980 and 31 December 2016. Articles on patients treated with parotidectomy and either END or ENI, and studies on nodal patterns of disease, were included. UK clinical oncologists were asked to complete an online questionnaire regarding their use of neck radiotherapy in this setting. RESULTS: From 96 references, 20 studies met the inclusion criteria: 11 reported on END, five on ENI and two on both. Eight studies reported on nodal patterns of disease. The prevalence of occult nodal metastases after END ranged from 0 to 45%. Five year locoregional control was variable (range 64-100%). For ENI, 5 year locoregional control varied from 74 to 100%. High-grade and T3/T4 tumours were factors for nodal relapse after END or ENI, which most commonly occurred in levels I-III. For the survey, 33/50 (66%) of cancer centres responded. Fourteen (42%) centres had guidelines for ENI. Most centres considered high-grade tumours (96%), T3/T4 disease (80%) and lymphovascular invasion (88%) as indications for ENI. Twelve centres (36%) irradiated levels Ib-IV electively; the remaining centres treated other various combinations of nodal levels. CONCLUSION: There is heterogeneity in the use and indications for ENI in the UK. ENI is a reasonable alternative to END as elective management for the cN0 neck in patients with high-grade tumours or T3/T4 disease. The elective clinical target volume should at least encompass nodal levels I-III.
Subject(s)
Lymphatic Irradiation/methods , Neck Dissection/methods , Neoplasm Recurrence, Local/therapy , Parotid Neoplasms/therapy , Combined Modality Therapy , Disease Management , Humans , Meta-Analysis as Topic , Neoplasm Recurrence, Local/pathology , Parotid Neoplasms/pathology , Prognosis , Retrospective StudiesABSTRACT
OBJECTIVES: Parameters have been derived in head and neck cancer to account for the additional biological effective dose provided by synchronous chemotherapy. The purpose of this study was to establish whether such parameters could be used to predict local control differences in anal cancer. METHODS: In anal cancer two randomised trials of radiotherapy vs chemoradiotherapy and two trials randomising between different synchronous chemotherapy regimens were identified. To predict differences in local control between the arms of the first two studies, a global value of 9.3 Gy for the chemotherapy biologically effective dose was employed. For the last two trials, values specific to differing chemotherapy schedules were derived. These values were added to the calculated biological effective dose for the radiotherapy component in order to predict local control outcomes in anal cancer trials. RESULTS: The predicted difference in local control using the global value of 9.3 Gy for the addition of synchronous chemotherapy in the trials of radiotherapy vs radiotherapy and synchronous chemotherapy was 24.6% compared with the observed difference of 21.4%. Using schedule-specific values for the contribution of chemotherapy, the predicted differences in local control in the two trials of differing synchronous chemotherapy schedules were 7.2% and 12% compared with the observed 18% and 0%. CONCLUSION: The methods initially proposed require modification to result in adequate prediction. If the decreased cisplatin dose intensity employed in anal cancer is modelled, more satisfactory predictions for such trials can be achieved. ADVANCES IN KNOWLEDGE: This revised modelling may be hypothesis generating.
Subject(s)
Anus Neoplasms/radiotherapy , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/methods , Head and Neck Neoplasms/therapy , Models, Biological , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Conformal/methods , Computer Simulation , Dose Fractionation, Radiation , Humans , Radiotherapy Dosage , Randomized Controlled Trials as TopicABSTRACT
AIMS: There has been a resurgence in interest in radiobiological modelling in head and neck cancer. The aim of this study was to determine if currently used parameters accurately predict both tumour and toxicity outcomes. MATERIALS AND METHODS: Trials were identified from a recent meta-analysis of altered fractionation. The tumour biologically effective dose (tBED; α/ß=10Gy, t(k) [onset time of accelerated repopulation]=22 days, t(p) [average doubling time during accelerated repopulation]=3 days, α=0.3Gy(-1)), acute mucosal biologically effective dose (amBED; α/ß=10Gy, t(k)=7 days, t(p)=2.5 days, α=0.3Gy(-1)) and late mucosal biologically effective dose (lmBED; α/ß=3Gy) were calculated for each arm of each trial. The correlation between the absolute percentage difference in BED between treatment arms and the observed percentage difference in local control, acute grade 3 mucositis and late grade 3 mucosal reaction was then assessed. RESULTS: A strong correlation was observed between the percentage difference in tBED and the percentage difference in local control (P=0.006). A trend towards a correlation was seen between the percentage difference in amBED and the percentage difference in acute grade 3 mucositis (P=0.06). A significant correlation was observed between the percentage difference in lmBED and the percentage difference in grade 3 late mucosal toxicity (P=0.02). However, a 15% decrease in lmBED between control and experimental arms of the study was necessary for any sparing of late mucosal toxicity to be observed. CONCLUSIONS: Currently used parameters for tumour accurately predict outcomes in randomised trials of altered fractionation. Although the relationship may be more complex for late mucosal reaction, the presence of a correlation is noteworthy given the infrequent reporting or occurrence of this toxicity. In the future, radiobiological modelling with the addition of volumetric parameters will be highly relevant, given attempts to dose escalate with intensity-modulated radiotherapy in poor risk patients and de-escalate in patients with an excellent prognosis.
Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/radiotherapy , Mucous Membrane/radiation effects , Radiobiology/trends , Radiotherapy, Intensity-Modulated , Acute Disease , Carcinoma, Squamous Cell/drug therapy , Combined Modality Therapy , Dose Fractionation, Radiation , Head and Neck Neoplasms/drug therapy , Humans , Models, Biological , Mucositis/etiology , Mucous Membrane/drug effects , Radiotherapy Dosage , Randomized Controlled Trials as Topic , Survival Rate , Treatment OutcomeABSTRACT
AIMS: Hypofractionated accelerated radiotherapy with concurrent carboplatin utilises both advantages of altered fractionation and synchronous chemotherapy to maximise local control in locally advanced head and neck cancer. Such fractionation schedules are increasingly used in the intensity-modulated radiotherapy era and the aim of this study was to determine the outcome of hypofractionated accelerated radiotherapy with carboplatin. MATERIALS AND METHODS: One hundred and fifty consecutive patients with squamous cell carcinoma of the larynx, oropharynx, oral cavity and hypopharynx (International Union Against Cancer [IUAC] stage II-IV) treated with 55Gy in 20 fractions over 25 days with concurrent carboplatin were analysed. Outcome measures were 2 year overall survival, local control and disease-free survival. RESULTS: The median follow-up in surviving patients was 25 months. IUAC stages: II n=15; III n=42; IV n=93. Two year overall survival for all patients was 74.9% (95% confidence interval 66.0-81.7%). Two year local control was 78.3% (95% confidence interval 69.6-84.8%). Two year disease-free survival was 67.2% (95% confidence interval 58.3-74.7%). There were 135 patients with stage III and IV disease. For these patients, the 2 year overall survival, local control and disease-free survival were 74.3% (95% confidence interval 64.7-81.6%), 79.1% (95% confidence interval 69.8-85.9%) and 67.6% (95% confidence interval 58.0-75.4%), respectively. Prolonged grade 3 and 4 mucositis seen at ≥4 weeks were present in 9 and 0.7%, respectively. Late feeding dysfunction (determined by dependence on a feeding tube at 1 year) was seen in 13% of the surviving patients at 1 year. CONCLUSION: Hypofractionated accelerated radiotherapy with concurrent carboplatin achieves a high local control. This regimen should be considered for a radiotherapy dose-escalation study using intensity-modulated radiotherapy.
Subject(s)
Antineoplastic Agents/therapeutic use , Carboplatin/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Radiotherapy, Intensity-Modulated , Adult , Aged , Combined Modality Therapy , Dose Fractionation, Radiation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Mucositis/etiology , Mucositis/prevention & control , Radiotherapy Dosage , Survival Rate , Treatment OutcomeABSTRACT
AIM: To evaluate the tolerability of synchronous chemotherapy and accelerated hypofractionated radiotherapy in patients with locally advanced squamous cell carcinoma of the base of the tongue. MATERIALS AND METHODS: Between 1999 and 2004, 43 patients with stage II-IV squamous cell carcinoma of the base of the tongue were treated with a combined modality of radiotherapy (prescribed 55 Gy in 20 fractions), synchronous chemotherapy and in some cases surgical neck dissection. End points were acute and late toxicity, 3 year locoregional control, overall survival, cancer-specific survival and compliance. RESULTS: The median follow-up for surviving patients was 3.9 years. All patients completed radiotherapy and 30% received neoadjuvant chemotherapy. The median time for the completion of treatment was 27 days (range 25-36). Overall, only 42% completed the prescribed synchronous chemotherapy. However, compliance increased to 60% in patients who did not receive neoadjuvant chemotherapy. Grade 3 mucositis developed in 90% of patients. Prolonged grade 3 mucositis (>4 weeks) was seen in 24/43 (56%) and none developed grade 4 mucositis. There were no toxic deaths. Feeding tube dependency at 1 year was 14%. The 3 year locoregional control, overall survival and cancer-specific survival were 70, 60 and 60%, respectively. Clinical T staging was most significantly associated with poor overall survival, cancer-specific survival and local control. Distant metastases occurred in 6/43 patients (14%), 5/6 without locoregional recurrence. CONCLUSION: The addition of synchronous chemotherapy to accelerated hypofractionated radiotherapy consistently led to grade 3 mucositis. Tumour control rates compare well with published outcomes. Higher mucosal toxicity and lower synchronous chemotherapy compliance compared with other series may suggest that this approach is at the limit of patient tolerability. However, the tumour site investigated and the choice of synchronous chemotherapy agent may also be important. Compliance may be improved using intensity-modulated radiotherapy and agents that do not enhance mucosal toxicity. Longer fractionation will probably increase compliance with chemotherapy, particularly when induction is used before synchronous treatment.
Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Squamous Cell/therapy , Radiotherapy/methods , Tongue Neoplasms/therapy , Adult , Aged , Antineoplastic Agents/adverse effects , Carcinoma, Squamous Cell/mortality , Combined Modality Therapy , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Tongue Neoplasms/mortalityABSTRACT
A better understanding of the molecular biology of renal cell carcinoma (RCC) and the emergence of tyrosine kinase inhibitors (TKIs) have revolutionized the treatment for patients with metastatic RCC (mRCC). Multikinase inhibitors (sunitinib and sorafenib) and the inhibitors of mammalian target of rapamycin (temsirolimus and everolimus) have recently shown superiority over IFN-alpha or placebo; and bevacizumab + IFN-alpha have demonstrated improved activity when compared to IFN-alpha alone in patients with mRCC. Newer anti-vascular endothelial growth factor (VEGF) agents such as axitinib, pazopanib and cediranib are currently under investigation to expand and elucidate future treatment options. Several studies have investigated the synergistic potential of TKIs with a view to blocking multiple signalling pathways simultaneously, but this approach has resulted in a significant increase in toxicity. Sequential TKI administration has demonstrated encouraging results but the optimal sequence of TKIs is yet to be determined. Studies combining TKIs with immunotherapy have resulted in varying degrees of success; with bevacizumab + IFN-alpha being the only studies with positive outcomes. The purpose of this review is to summarize the current evidence supporting the role of TKIs and to discuss potential future directions in the management of mRCC. The role of TKIs as monotherapy, in combination with immunotherapy or other TKIs (combined or sequential approach) will be discussed.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers/blood , Biomarkers/metabolism , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/secondary , Humans , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Kidney Neoplasms/diagnosis , Kidney Neoplasms/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/drug effects , Sirolimus/pharmacology , Sirolimus/therapeutic use , TOR Serine-Threonine Kinases , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/metabolismABSTRACT
AIMS: To model the therapeutic gain from the addition of synchronous chemotherapy to radiotherapy in locally advanced head and neck cancer. MATERIALS AND METHODS: Refinements to previous methodology, including the derivation of weighted estimates of key parameters from randomised studies and the use of the expected mucosal biologically effective dose concept, have been used to produce an evidence-based assessment of the benefit from the addition of chemotherapy when considering acute grade 3 mucositis and rates of 5-year local control. RESULTS: For a value of alpha=0.3Gy(-1) the additional contribution from chemotherapy to local control was estimated to be 9.3Gy(10) and to grade 3 mucositis 6.4Gy(10). The additional expected mucosal biologically effective dose if radiotherapy dose escalation had been used instead of chemotherapy would have been 11.6Gy(10). Therefore, the mucosal sparing by using synchronous chemotherapy rather than radiotherapy dose escalation was found to be 5.2Gy(10) or the equivalent dose in 2Gy fractions 4.3Gy EQD(2). CONCLUSION: This modelling suggests a small therapeutic gain for the use of synchronous chemotherapy instead of radiotherapy dose escalation. This conclusion is dependent on the linear quadratic model and takes no account of late side-effects. This gain would be greater for agents that enhance the mucosal reaction to a lesser degree. This gain may be less when data for radiotherapy dose escalation to smaller high dose volumes using intensity-modulated radiotherapy are considered.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Models, Biological , Combined Modality Therapy , Humans , Mucositis/prevention & control , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Randomized Controlled Trials as Topic , Survival Rate , Treatment OutcomeABSTRACT
AIMS: To review the results of hypofractionated radiotherapy in T1N0M0 squamous cell carcinoma of the larynx. MATERIALS AND METHODS: A series of 100 patients treated with radiotherapy between 1993 and 2001 was reviewed. The median age was 67 years. The median follow-up was 7 years (range 3-14 years). Radiotherapy was delivered to a total dose of 50 Gy in 16 fractions treating daily, 5 days a week over 21 days. RESULTS: Locoregional control rates with radiotherapy alone were 92% at 2 years and 88% at 5 years. After salvage surgery, the ultimate locoregional control rate was 96%. The relapse-free survival rates at 2 and 5 years were 85 and 70%, respectively. The cause-specific survival rates at 2 and 5 years were 99 and 97%, respectively. Overall survival rates at 2 and 5 years were 91 and 76%, respectively. Second primary cancers occurred in 21% of patients, primarily in the lung. CONCLUSIONS: Radiotherapy to a total dose of 50 Gy in 16 fractions for T1N0M0 squamous cell carcinoma of the larynx offers high locoregional control rates with voice preservation. These results from a hypofractionated radiotherapy schedule are comparable with other longer fractionation schedules and offer potential for optimising resource usage.
Subject(s)
Laryngeal Neoplasms/radiotherapy , Neoplasms, Squamous Cell/radiotherapy , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Dose Fractionation, Radiation , Female , Follow-Up Studies , Humans , Laryngeal Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Neoplasms, Squamous Cell/pathology , Treatment OutcomeABSTRACT
AIM: To examine the feasibility and determine the maximum tolerated dose of outpatient carboplatin given with synchronous hypofractionated accelerated radiotherapy for squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: Patients with stages II-IV SCCHN and unresected primary tumour were treated with synchronous carboplatin given in an outpatient setting on day 1 and day 21 in cohorts of three to six patients with incremental area under curve (AUC) factors commencing at 3.5. Grade 3 mucositis persisting for 4 weeks in two patients in a cohort was considered dose limiting. RESULTS: A total of 19 patients were enrolled and assessable for toxicity. All 19 patients completed 55 Gy of radiotherapy and were assessable for response. Grade 3 mucositis lasting 4 weeks or more was seen in three patients, two of them received AUC 5 carboplatin. A complete response was seen in 16 patients, with a further patient having a partial response, giving a response rate of 89%. With a median follow-up of 24 months (range 11-30 months), 13 patients were alive with no evidence of recurrent disease. Local recurrence had occurred in four patients with distant spread in three patients. CONCLUSION: Carboplatin with concurrent hypofractionated accelerated radiotherapy is feasible for patients with advanced SCCHN and good performance status. The recommended phase II dose of carboplatin given in week 1 and week 4 with 55 Gy in 20 fractions is AUC 4.5.
Subject(s)
Antineoplastic Agents/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Dose Fractionation, Radiation , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Adult , Aged , Analgesics, Opioid/therapeutic use , Antineoplastic Agents/adverse effects , Area Under Curve , Carboplatin/adverse effects , Combined Modality Therapy , Dose-Response Relationship, Drug , Humans , Infusions, Intravenous , Middle Aged , Mucositis/drug therapy , Mucositis/etiology , Neoplasm Recurrence, Local , Neoplasm Staging , Treatment OutcomeABSTRACT
AIMS: To review our treatment strategy and outcomes for metastatic squamous cell carcinoma of the neck. METHODS: One hundred and six consecutive patients treated between 1992 and 1998 were analysed retrospectively. The following data were obtained. Demographic details, tumour site, clinical and pathological TMN staging, tumour grade and presence of extracapsular spread, treatment modality (surgery, radiotherapy and chemotherapy), type of neck dissection and complications, 2-year loco-regional control and 5-year overall survival. RESULTS: Ninety-two patients had advanced disease (stages 3 and 4) and of these, 57% had palpable neck metastases. One hundred and six patients underwent a total of 132 neck dissections. Seventy-three patients had post-operative radiotherapy to both sides of the neck and a total of 31 patients took part in the UKHAN 1 trial. Seventy percent of patients achieved 2-year loco-regional control and 63% survived 5-years. CONCLUSION: Metastatic squamous cell carcinoma of the neck can successfully be treated with an aggressive surgical approach and post-operative radiotherapy when indicated. Excellent 2-year loco-regional control and 5-year survival rates are possible.
Subject(s)
Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms/surgery , Neck Dissection , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Chemotherapy, Adjuvant , Chi-Square Distribution , Combined Modality Therapy , Female , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , Neoplasm Staging , Postoperative Complications , Prognosis , Proportional Hazards Models , Radiotherapy, Adjuvant , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: The addition of short course pre-operative radiotherapy to total mesorectal excision reduces local recurrence in resectable adenocarcinoma of the rectum. In a previous retrospective study potential factors associated with early complications following this combination were identified. The aim of this study was to examine these relationships in a prospective multicentre audit. METHODS: One hundred and seven patients who received short course pre-operative radiotherapy in four cancer centres between 1 October 2001 and 30 September 2002 were included. Data including patient age, radiotherapy field length, overall treatment time, operation type, surgical outcomes and complications occurring within 3 months of the 1st day of radiotherapy were collected. These were compared and combined with the previously studied cohort of 176 patients treated at one centre between 1st January 1998 and 31st December 1999. RESULTS: In the prospective cohort only patient age (P=0.001) was significantly associated with acute complications. However, both the overall treatment time (median 9.0 vs 11.0 days P <0.0001) and field length (median 16.6 vs 17.0 cm P=0.03) were significantly shorter in this cohort when compared to the previous retrospective study. In patients from both studies (n=283), increasing age (P=0.002) and field length (independent of operation type) (P=0.02) were independently associated with an increased risk of acute complications. CONCLUSIONS: This study suggests that meticulous selection of patients for short course pre-operative radiotherapy and smaller planning target volumes may be associated with a lower risk of acute complications. The use of MRI scanning to stage pelvic disease may reduce the number of patients with R1 resections receiving short course pre-operative radiotherapy.
Subject(s)
Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Postoperative Complications , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery , Acute Disease , Adenocarcinoma/pathology , Age Factors , Dose Fractionation, Radiation , Female , Humans , Male , Medical Audit , Neoplasm Staging , Prospective Studies , Radiotherapy, Adjuvant/methods , Rectal Neoplasms/pathology , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
We conducted a phase I/II study investigating synchronous chemoradiotherapy with mitomycin C and infusional 5-fluorouracil (5-FU) in muscle invasive bladder cancer. Early dose escalation results were previously published. We report the long-term toxicity and efficacy results with the optimised regimen. Patients with muscle invasive bladder cancer with glomerular filtration rate >25 ml min(-1) were eligible. Mitomycin (12 mg m(-2) on day 1 only) and infusional 5-FU (500 mg m(-2) day(-1)) for 5 days were administered during weeks 1 and 4 of radiotherapy of 55 Gy in 20 fractions. A total of 41 patients were enrolled, median age was 68 years, 33 were male and eight female patients. Out of the 41 patients, 20 (49%) had hydronephrosis at presentation and 25 (62%) had T3b or T4 disease. Four patients experienced Grade III thrombocytopenia and three patients had Grade III neutropenia. There were no episodes of febrile neutropenia. Four patients experienced Grade III diarrhoea and 1 Grade III urgency and dysuria. Six patients did not undergo cystoscopic evaluation due to early metastatic spread although there was no clinical suggestion of bladder failure. In all, out of 35 evaluable patients, 25 (71%) had macroscopic complete response at 3-month cystoscopy, and biopsy confirmed in 24 out of 25. A total of 16 (39%) patients remain alive with a median follow-up of 50.7 (range 23.5-68.8) months, 14 with a functioning bladder with no reported long-term treatment-related bladder or bowel toxicity. Five out of 41 patients have undergone salvage cystectomy: two for persistent CIS, two T1 and one muscle invasive recurrence. Four patients have received intravesical chemotherapy, of whom two remain alive with a functioning bladder. Overall 12-, 24- and 60-month (m) survival rates were 68, 49 and 36%. Local and distant progression free rates were 82 and 86% at 12-m and 79 and 75% at 24-m. Organ preservation using multimodality therapy is feasible and safe, even in patients with poor renal reserve, and does not compromise salvage therapies. A national phase III trial BC2001 (www.bc2001.org.uk) exploring the effects of synchronous chemoradiotherapy with this regimen is currently recruiting.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/radiotherapy , Neoplasm Invasiveness , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/radiotherapy , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Transitional Cell/pathology , Combined Modality Therapy , Dose Fractionation, Radiation , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Kidney/drug effects , Kidney/physiology , Male , Middle Aged , Mitomycin/administration & dosage , Neoplasm Recurrence, Local , Neutropenia/chemically induced , Survival Analysis , Thrombocytopenia/chemically induced , Treatment Outcome , Urinary Bladder Neoplasms/pathologyABSTRACT
AIMS: No randomised trials have addressed the use of external beam radiotherapy (EBRT) in the treatment of differentiated thyroid cancer. The indications for EBRT, the technique and recommended dose all remain controversial. MATERIALS AND METHODS: We included patients treated with EBRT with curative intent from two cancer centres between 1988 and 2001. Data were collected from hospital notes, radiotherapy prescriptions and local cancer registry. RESULTS: The indications for treatment in the 41 identified patients were macroscopic residual disease 23 (56%), microscopic residual disease 10 (25%), Hurthle cell variants 3 (7%), multiple lymph-node involvement 3 (7%) and other 2 (5%). Delivered doses ranged from 37.5-66 Gy over 3-6.5 weeks. Rate of local recurrence and overall survival at 5 years were as follows: papillary 26% and 67%; follicular 43% and 48%; well differentiated 21% and 67%; focus of poor differentiation/Hurthle cell variants 69% and 32%; complete excision 25% and 61%; residual disease 37% and 59%; EBRT total dose < 50 Gy 63% and 42%; 50-54 Gy 15% and 72%; > 54 Gy 18%, and 68%. CONCLUSIONS: The results in this study are consistent with previous retrospective studies of EBRT. The wide range of indications and doses used with radical intent highlights the lack of clinical and radiobiological data on the response of differentiated thyroid cancer to EBRT. Despite the small study size, the 5-year local recurrence results indicate a possible dose response within the dose range used.
Subject(s)
Carcinoma, Papillary, Follicular/radiotherapy , Thyroid Neoplasms/radiotherapy , Carcinoma, Papillary, Follicular/mortality , Carcinoma, Papillary, Follicular/secondary , Confidence Intervals , Female , Follow-Up Studies , Humans , Incidence , Lymphatic Metastasis , Male , Neoplasm Recurrence, Local/epidemiology , Radiotherapy, Conformal/methods , Retrospective Studies , Survival Analysis , Survival Rate , Thyroid Neoplasms/mortality , United Kingdom/epidemiologyABSTRACT
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 & dosageABSTRACT
The aim of this paper was to evaluate our experience using conservation surgery in the management of T1 and T2 oropharyngeal squamous cell carcinoma. Eighteen patients underwent conservation surgery between 1993 and 2000 and were analysed retrospectively. The mean age was 54 years and the male to female ratio was 8:1. There were 14 tonsil and 4 tongue base tumours and 83% of cases presented with neck nodes, thereby classifying them as having advanced disease (stages 2-4). All patients received postoperative radiotherapy. All patients were followed up to December 2001. The median follow-up time was 3.8 years (minimum was 1.5 years). The 2-year and 5-year survival rates were 100% and 92% respectively. Approximately 66% of patients returned the EORTC and GHQ/12 quality-of-life questionnaires. Of these, seventy-five percent had a high healthy level of general functioning in accordance with the EORTC general health section. These results show that conservation surgery techniques are effective in the treatment of T1 and T2 oropharyngeal squamous carcinoma associated with significant metastatic neck disease. The techniques are well tolerated, produce minimal functional deficit and do not have a negative impact on the patients quality of life in either the immediate postoperative period or up to 4 years post-treatment.
Subject(s)
Carcinoma, Squamous Cell/surgery , Oropharyngeal Neoplasms/surgery , Adult , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/radiotherapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/pathology , Oropharyngeal Neoplasms/radiotherapy , Quality of Life , Radiotherapy, Adjuvant , Tongue Neoplasms/pathology , Tongue Neoplasms/surgery , Tonsillar Neoplasms/pathology , Tonsillar Neoplasms/surgeryABSTRACT
Patients with recurrent or refractory head and neck squamous cell carcinoma received cisplatin/epinephrine injectable gel or placebo gel injected directly into the clinically dominant tumour. The double-blind phase III trial comprised of up to 6 weekly treatments over 8 weeks, 4 weekly evaluation visits, and then monthly follow-up; open-label dosing began as needed after three blinded treatments. Tumour response was defined as complete (100% regression) or partial (50-99% regression) sustained for > or =28 day, and patient benefit as attainment of palliative or preventive goals prospectively selected by investigators and patients. With cisplatin/epinephrine gel, 25% (14 out of 57) of tumours responded (16% complete regression, 9% partial regression), vs 3% (one out of 35, complete regression) with placebo (P=0.007). Patient benefit was positively associated with target tumour response in the blinded period among cisplatin/epinephrine gel recipients (P=0.024): 43% (six out of 14) of responders benefited, vs 12% (five out of 43) of non-responders. The most frequent adverse event was pain during injection and the next most frequent was local cytotoxic effects consistent with the gel's mode of action. Systemic adverse events typical of intravenous cisplatin were uncommon. Intratumoural therapy with cisplatin/epinephrine gel provided safe, well-tolerated, effective palliative treatment for patients with locally advanced head and neck squamous cell carcinoma, who lack other satisfactory treatment options.
Subject(s)
Adrenergic Agonists/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Cisplatin/therapeutic use , Epinephrine/therapeutic use , Head and Neck Neoplasms/drug therapy , Adrenergic Agonists/administration & dosage , Adrenergic Agonists/adverse effects , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Carcinoma, Squamous Cell/secondary , Cisplatin/administration & dosage , Cisplatin/adverse effects , Double-Blind Method , Drug Combinations , Epinephrine/administration & dosage , Epinephrine/adverse effects , Female , Gels , Head and Neck Neoplasms/pathology , Humans , Injections, Intralesional , Male , Middle Aged , Prospective Studies , Safety , Treatment OutcomeABSTRACT
We report the case history of two patients treated with primary gastric irradiation for localized low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach that failed to respond to anti-Helicobacter pylori antibiotics. One patient refused gastrectomy and the other was considered unfit for surgery. Both patients obtained a biopsy-confirmed complete response and are well and disease free after a median follow-up time of 28 months. A review of the literature on the treatment options for this condition has been undertaken. Gastric irradiation is an effective and safe alternative to gastrectomy in the treatment of low-grade MALT lymphoma of the stomach with the added advantage of organ preservation.
Subject(s)
Lymphoma, B-Cell, Marginal Zone/radiotherapy , Stomach Neoplasms/radiotherapy , Aged , Anti-Bacterial Agents/therapeutic use , Disease-Free Survival , Gastrectomy , Helicobacter Infections/complications , Helicobacter pylori/pathogenicity , Humans , Lymphoma, B-Cell, Marginal Zone/pathology , Male , Middle Aged , Stomach Neoplasms/pathology , Treatment OutcomeABSTRACT
BACKGROUND: The management of locally advanced bladder cancer remains controversial with poor local control with radiotherapy alone. Synchronous chemotherapy regimens have yielded encouraging results in other primary sites. PATIENTS AND METHODS: Patients with T2-T4a N0/NX M0 bladder cancer were entered into this single centre phase I-II study. Patients received radiotherapy to 55 Gy in 20 fractions over four weeks. Concurrent chemotherapy was given with Mitomycin C 12 mg/m2 day 1 and 5-fluorouracil 500 mg/m2/24 hours weeks one and four of radiotherapy for five or seven days on each occasion. RESULTS: Thirty-one patients entered the trial from March 1998 to December 1999 (22: 5-day; 9: 7-day schedule). Median age was 68 (range 58-79) years, 23 males and 8 females. T2: 9 (29%); T3a: 4 (12%); T3b: 9 (29%); T4: 9 (29%); TCC grade 2: 8 (26%) and grade 3: 23 (74%); 14 of 31 had hydronephrosis. Ten of thirty-one had a GFR < 50 ml/min. Toxicity was mild to moderate with the five-day schedule. More severe toxicity was seen with the seven-day schedule: five of nine patients failed to complete planned therapy. Pathological complete response rate at three months was 74% (5-day regimen) and 50% (7-day regimen). Overall 12-month survival was 65%. CONCLUSION: Chemoradiotherapy with the five-day schedule is feasible with acceptable toxicity in poor prognosis patients. A randomised trial is being launched.