Gender-specific activity of chemotherapy correlates with outcomes in chemosensitive cancers of young adulthood.

Good evidence indicates that adolescents and young adults (AYAs) with cancer do badly compared with children with similar cancers. The reasons are poorly understood. Australian registry data on 14,824 cancers of adolescence and young adulthood seen between 1982 and 2002 were reviewed. A detailed substudy of clinical characteristics was analyzed from 179 AYAs with Hodgkin lymphoma (HL), Ewing sarcoma (ES) or osteosarcomas (OS) treated at a single institution. Despite significant improvements in survival for both groups over the period in question, for acute lymphoblastic leukaemia, rhabdomyosarcoma, ES, OS and HL, survival for AYAs was worse than for children. For ES, OS and HL, the survival gap occurred almost entirely in males (Hazard ratios compared with female AYAs of 1.8 [p < 0.01], 1.4 [p = 0.03] and 1.5 [p < 0.01] respectively). Survival outcomes from ES, OS and HL for female AYAs were not significantly different from children of either sex. For brain tumors and thyroid cancers, which are primarily treated surgically, there were no gender-related differences in outcomes. Although no differences in tumor stage or compliance were identified, male AYAs experienced less toxicity and lower response rates to chemotherapy (p = 0.008). Young males account almost entirely for excess mortality from chemosensitive cancers of adolescence and young adulthood compared to children, which may be due to relative underdosing with current chemotherapy dosing algorithms.

Follow up results of a prospective study to evaluate the impact of FDG-PET on CT-based radiotherapy treatment planning for oesophageal cancer.

BACKGROUND: This prospective study aims to determine the impact of PET/CT on radiotherapy planning and outcomes in patients with oesophageal cancer. METHODS: All patients underwent PET/CT scanning in the radiotherapy treatment position, and received treatment planned using the PET/CT dataset. GTV was defined separately on PET/CT (GTV-PET) and CT (GTV-CT) datasets. A corresponding PTV was generated for each patient. Volumetric and spatial analysis quantified the proportion of FDG-avid disease not included in CT-based volumes. Clinical data was collected to determine locoregional control and overall survival rates. RESULTS: 13 (24.1%) of 57 accrued patients had metastatic disease detected on PET. Median follow up was 4 years. FDG-avid disease would have been excluded from GTV-CT in 29 of 38 patients (76%). In 5 patients, FDG-avid disease would have been completely excluded from the PTV-CT. GTV-CT underestimated the cranial and caudal extent of FDG-avid tumour in 14 (36%) and 10 (26%) patients. 4-Year overall survival and locoregional failure free survival were 37% and 65%. CONCLUSIONS: PET/CT altered the delineation of tumour volumes when compared to CT alone, and should be considered standard for treatment planning. Although clinical outcomes were not improved with PET/CT planning, it did allow the use of smaller radiotherapy volumes.

A prospective study to evaluate the impact of FDG-PET on CT-based radiotherapy treatment planning for oesophageal cancer.

BACKGROUND AND PURPOSE: This prospective study sought to determine how the use of combined PET/CT for radiotherapy treatment planning of oesophageal cancer would alter the delineation of tumour volumes compared to CT alone if PET/CT is assumed to more accurately represent true disease extent. PATIENTS AND METHODS: All patients underwent FDG-PET/CT scanning in the radiotherapy treatment position. For each patient, two separate gross tumour volumes (GTV) were defined, one based on CT images alone (GTV-CT) and another based on combined PET/CT data (GTV-PET). Corresponding planning target volumes (PTV) were generated, and separate treatment plans were then produced. For each patient, volumetric analysis of GTV-CT, PTV-CT and GTV-PET was performed to quantify the proportion of PET-avid disease that was not included in the GTV and PTV (geographic miss) if CT data alone were used for radiotherapy planning. Assessment of the cranial and caudal extent of the primary oesophageal tumour as defined by CT alone vs PET/CT was also compared. RESULTS: The addition of PET information altered the clinical stage in 8 of 21 eligible patients enrolled on the study (38%); 4 patients had distant metastatic disease and 4 had unsuspected regional nodal disease. Sixteen patients proceeded to the radiotherapy planning phase of the study and received definitive chemoradiation planned with the PET/CT data set. The GTV based on CT information alone excluded PET-avid disease in 11 patients (69%), and in five patients (31%) this would have resulted in a geographic miss of gross tumour. The discordance between CT and PET/CT was due mainly to differences in defining the longitudinal extent of disease in the oesophagus. The cranial extent of the primary tumour as defined by CT vs PET/CT differed in 75% of cases, while the caudal extent differed in 81%. CONCLUSIONS: This study demonstrates that if combined PET/CT is used for radiotherapy treatment planning, there may be alterations to the delineation of tumour volumes when compared to CT alone, with the potential to avoid a geographic miss of tumour.

Post-radiation sarcoma of the neck treated with re-irradiation followed by wide excision.

BACKGROUND: Post-radiation sarcoma (PRS) is an uncommon disease manifesting as sarcoma in a previously irradiated field, usually with a latent period of 5 years or more. Literature is limited to small series. Optimal management of this disease is unclear. Positive margins are common following attempted curative surgery and outcomes are poor. Radiotherapy is hardly used and its effect on PRS is not known. We described a case of PRS treated with preoperative radiotherapy followed by margin-negative wide excision. CASE PRESENTATION: The 59-year-old patient presented with a mass in the left supraclavicular fossa and numbness in the arm, six years following radical irradiation of the head and neck for nasopharyngeal carcinoma. Open biopsy showed pleomorphic spindle cell sarcoma. She was treated with pre-operative hyperfractionated radiotherapy followed by margin-negative wide excision and nerve grafting. Cumulative radiation dose to the supraclavicular fossa was 98 Gy. Histological examination of the post-irradiation tumor specimens showed evidence of significant tumor response to re-irradiation. The patient remained free of disease five years after surgery with excellent functional outcome. CONCLUSION: Role of radiotherapy in PRS is uncertain. We described a case that was successfully managed with preoperative radiotherapy and margin-negative wide excision in terms of tumor control and functional outcomes. The impact of radiotherapy was demonstrated in the post-irradiation resected specimen. Further investigation using re-irradiation and surgery in PRS is warranted.

3D conformal radiotherapy for gastric cancer--results of a comparative planning study.

BACKGROUND AND PURPOSE: Many radiation oncologists are reluctant to use anteroposterior-posteroanterior (AP-PA) field arrangements when treating gastric cancer with adjuvant postoperative radiotherapy due to concerns about normal tissue toxicity, particularly in relation to the kidneys and spinal cord. In this report, we describe a multiple-field conformal radiotherapy technique, and compare this technique to the more commonly used AP-PA technique that was used in the recently reported Intergroup study (INT0116). MATERIALS AND METHODS: Fifteen patients with stages II-IV adenocarcinoma of the stomach were treated with adjuvant postoperative chemoradiotherapy using a standardised 3D conformal radiotherapy technique that consisted of a 'split-field', mono-isocentric arrangement employing 6 radiation fields. For each patient, a second radiotherapy treatment plan was generated utilising AP-PA fields. The two techniques were then compared for target volume coverage and dose to normal tissues using dose volume histogram (DVH) analysis. RESULTS: The conformal technique provides more adequate coverage of the target volume with 99% of the planning target volume (PTV) receiving 95% of the prescribed dose, compared to 93% using AP-PA fields. Comparative DVHs for the right kidney, left kidney and spinal cord demonstrate lower radiation doses using the conformal technique, and although the liver dose is higher, it is still well below liver tolerance. CONCLUSIONS: 3D conformal radiotherapy produces superior dose distributions and reduced radiation doses to the kidneys and spinal cord compared to AP-PA techniques, with the potential to reduce treatment toxicity.

Phase II trial of continuous infusion carboplatin, 5-fluorouracil, and radiotherapy for localized cancer of the esophagus.

The aim of this study was to determine the toxicity, response rate, failure-free survival, and overall survival in a treatment program comprising continuous infusion carboplatin, short in-fusion 5-fluorouracil (5-FU) and radiotherapy for localized carcinoma of the thoracic esophagus. To be eligible, patients were required to have Karnofsky performance status greater than or equal to 60, adequate organ function, and have received no prior therapy. Planned radiation dose was 50 Gy in 25 fractions over 5 weeks. 5-FU was to be administered commencing days 1 and 29 of radiotherapy, and given at a dose of 1 g/m2/d for 4 days as a continuous infusion. Carboplatin was to commence on day 1 of radiotherapy and be given throughout the period of radiation as a continuous infusion. The starting dose of carboplatin was 28 mg/m2/d. The protocol specified a 25% dose reduction of carboplatin if more than two of the first six patients experienced dose-limiting toxicity (DLT). DLT was defined as grade IV neutropenia lasting more than 7 days, grade IV thrombocytopenia, or any grade IV nonhematologic toxicity. All 23 patients in the study received protocol radio-therapy, except one who was given an extra 10 Gy. Seven patients received carboplatin at 28 mg/m2/d and 16 received 21 mg/m2/d. Hematologic DLTs were experienced by all of the seven patients receiving the higher dose. No patients in the low-dose group experienced hematologic DLTs, and only 2 of 16 ceased chemotherapy early because of myelosuppression. Three patients in the low-dose group experienced grade IV esophagitis but were able to complete protocol radiotherapy. Apart from esophagitis, nonhematologic toxicity was generally moderate or mild. Six patients had thrombosis complicating the central venous catheters. Endoscopy was performed in 21 patients (91%), with an overall complete response rate of 65% (CI: 43-84%) for the whole group or 71% (CI: 48-89%) for the endoscopically evaluated group. Estimated median failure-free survival time was 8.9 months (CI: 7.1-12.9), and estimated median overall survival time was 21.4 months (CI: 9.6 -35.4). Carboplatin at 21 mg/m2/d as a continuous infusion may be given safely in combination with short infusional 5-FU and radiotherapy for localized carcinoma of the esophagus. This combination has resulted in response data comparable to that of larger studies of cisplatin-containing regimens and warrants further study, ideally in a phase III randomized controlled trial.

Once-daily reirradiation for rectal cancer in patients who have received previous pelvic radiotherapy.

INTRODUCTION: The purpose of this study is to assess the efficacy and toxicity using once-daily reirradiation for patients with rectal cancer having received previous pelvic radiotherapy. METHOD: Between June 1997 and June 2008, 56 patients were identified having received previous pelvic radiotherapy and received reirradiation for rectal cancer. Reirradiation intent was palliative in 43 patients, and preoperative/postoperative in 13 patients. Eighty per cent of patients received concurrent chemotherapy (n = 45). RESULTS: The median dose-fractionation reirradiation schedule was 39.6 Gy in 22 fractions once daily (range 20-39.6 Gy), and the median cumulative radiation dose was 87.3 Gy. Seven patients experienced a grade 3 acute toxicity, with no grade 4 event. Fifty-one patients (91%) completed the treatment and five patients required a treatment break. The overall symptomatic response rate was 88% at three months post-reirradiation. There was one late effect of skin ulceration among patients reirradiated palliatively. Median overall survival was 39 months in patients undergoing radical surgery versus 15 months in patients reirradiated palliatively (P < 0.001). CONCLUSION: Once-daily reirradiation to a total dose of ≤39.6 Gy is relatively safe in the treatment of patients with rectal cancer after previous pelvic radiotherapy. It is effective in symptom control and provides an additional option in management of local recurrence.

Surgical outcome of soft tissue sarcomas of the adductor compartment.

PURPOSE: To review outcomes and complications of 25 consecutive patients with soft tissue sarcomas in the adductor compartment. METHODS: Records of 11 men and 14 women aged 20 to 83 (mean, 56) years who underwent resection for soft tissue sarcomas in the adductor compartment were reviewed. Two of the patients had undergone inadequate resection of the tumour elsewhere. No patient had metastases. 20 and 2 patients underwent neo-adjuvant and postoperative radiotherapy, respectively. The interval between radiotherapy and surgery was at least 3 weeks. No neo-adjuvant chemotherapy was given. 24 patients underwent limb salvage surgery and one had external hemipelvectomy. 21 patients had direct wound closure; in 4 a microsurgical free flap was used. RESULTS: The overall survival rate was 81% and 72% at 3 and 5 years, respectively, and remained unchanged until the end of follow-up. Four patients died from pulmonary metastases and one died from liver metastases. One patient had local recurrence, and 7 (26%) developed major complications. Five patients underwent revision surgery. CONCLUSION: Good survival and local control rates can be achieved in patients with soft tissue sarcomas in the adductor compartment using limb salvage and radiotherapy.

Promising results of a cooperative group phase II trial of preoperative chemoradiation for locally advanced rectal cancer (TROG 9801).

PURPOSE: This article reports the overall survival, failure-free survival, local failure, and late radiation toxicity of a phase II trial of preoperative radiotherapy with continuous infusion 5-fluorouracil for rectal cancer after a minimum 3.5 years of follow-up. METHODS: Eligible patients were those with newly diagnosed localized adenocarcinoma of the rectum, within 12 cm of the anal verge, staged T3-T4 and deemed suitable for curative resection. Radiotherapy (50.4 Gy in 28 fractions in five weeks and three days) was given with continuous infusion 5-fluorouracil throughout the course of radiotherapy. RESULTS: A total of 82 patients were accrued in 13 months. The median follow-up time was 4.1 (range, 2.3-4.5) years. There were 55 males (67 percent) and the median age was 59 (range, 27-87) years. Patients were staged pretreatment as T3 (89 percent) and resectable T4 (11 percent). Endorectal ultrasound was performed in 70 percent and magnetic resonance imaging in another 5 percent. The four-year overall and failure-free survival rates were 82 percent (95 percent CI: 72-89) and 69 percent (95 percent CI: 58-78), respectively. The cumulative incidence of local failure at four years was 3.9 percent (95 percent CI: 1.3-11). Risk of failures, local and distant, has not reached a plateau phase. CONCLUSION: This regimen can be delivered safely and without leading to a significant increase in late toxicity. It provides excellent local control and favorable overall survival. There is a need for longer follow-up than has commonly been used for the proper evaluation of failures after an effective regimen of preoperative chemoradiation.