Long-term follow up after allogeneic stem cell transplantation in patients with severe aplastic anemia after cyclophosphamide plus antithymocyte globulin conditioning.

BACKGROUND: Due to increased rates of secondary solid organ cancer in patients with severe aplastic anemia who received an irradiation-based conditioning regimen, we decided some years ago to use the combination of cyclophosphamide and antithymocyte globulin. We report the long-term follow up of patients who underwent hematopoietic stem cell transplantation from an HLA-matched sibling donor after this conditioning regimen. DESIGN AND METHODS: We analyzed 61 consecutive patients transplanted from June 1991 to February 2010, following conditioning with cyclophosphamide (200 mg/kg) and antithymocyte globulin (2.5 mg/kg/day × 5 days). RESULTS: Median age was 21 years (range 4-43); 41 of the 61 patients were adults. Median duration of the disease before hematopoietic stem cell transplantation was 93 days. All but 2 patients received bone marrow as the source of stem cells and all but 2 engrafted. Cumulative incidence of acute grade II-IV graft-versus-host disease was 23% (95%CI 13-34) and 18 developed chronic graft-versus-host disease (cumulative incidence 32% at 72 months, 95% CI 20-46). In multivariate analysis, a higher number of infused CD3 cells was associated with an increased risk of developing chronic graft-versus-host disease (P = 0.017). With a median follow up of 73 months (range 8-233), the estimated 6-year overall survival was 87% (95% CI 78-97). At 72 months, the cumulative incidence of avascular necrosis was 21% and 12 patients presented with endocrine dysfunction (cumulative incidence of 19%). Only one patient developed a secondary malignancy (Hodgkin's lymphoma) during follow up. CONCLUSIONS: Cyclophosphamide and antithymocyte globulin is an effective conditioning regimen for patients with severe aplastic anemia and is associated with low treatment-related mortality. Long-term complications include avascular necrosis and endocrine dysfunction.

High-dose-rate brachytherapy boost to the dominant intra-prostatic tumor region: hemi-irradiation of prostate cancer.

BACKGROUND: To assess the feasibility, toxicity, and outcome of prostate hemi-irradiation with a high-dose-rate brachytherapy (HDR-BT) boost for patients presumed to harbor dominant intra-prostatic tumors in a single lobe. METHODS: After 3D conformal external radiotherapy (3DCRT) to 64-64.4 Gy, 77 patients with non-metastatic locally aggressive prostate cancer have been treated from 2000 to 2004, with HDR-BT using temporary open MRI-guided (192) Ir implants, to escalate the dose in the boost region. Twenty patients (26%) had one lobe involvement (i.e., one sided endorectal MRI, rectal examination, and biopsies) and were boosted to one side of the gland only. A dose of 12, 14, and 16 Gy in two fractions was delivered to 5, 6, and 9 patients, respectively. RESULTS: After a median follow-up 69 months, no differences in late rectal toxicity were observed between the unilaterally and bilaterally irradiated cohorts. Although, grade 2 late urinary toxicity was worse in the hemi-irradiated group (P = 0.03), severe grade ≥3 late urinary toxicity at 5 years was not different: 10% versus 8.8% in the unilaterally and bilaterally irradiated cohorts, respectively. Grade 4 late urinary toxicity, however, was exclusively observed in patients boosted to both lobes (5/57, 8.8%). Five-year biochemical relapse-free survival was 79.7% versus 70.5% for the unilateral and bilateral boost groups, respectively (P = 0.99). CONCLUSION: Prostate hemi-irradiation with a HDR-BT boost to the dominant tumor region may be considered when rectal examination, MRI, and biopsies suggest one lobe involvement. Nevertheless, strict dosimetric optimization is needed in order to further reduce the risk of late severe toxicity.

Outcome and risk factors for late-onset complications 24 months beyond allogeneic hematopoietic stem cell transplantation.

OBJECTIVES: The aim of this retrospective study was to assess the incidence of late complications occurring ≥2 years after allogeneic hematopoietic stem cell transplantation (HSCT) for malignant diseases using a T-cell depletion strategy. METHODS: Between 1984 and 2004, 142 patients were eligible for the study. Total body irradiation (TBI) was carried out in 85% of the patients and T-cell depletion in 84%. RESULTS: Non-relapse mortality (NRM) was 3% (95% CI 0-11) at 10 years, and serious late events affected a substantial number of patients. The cumulative incidence (CI) of chronic graft-versus-host disease (cGvHD) was 30% (95% CI 23-40), and that of infectious complications was 17% (95% CI 11-23). Multivariate analysis showed a higher risk for late complications in patients with cGvHD (HR 1.9, 95% CI 1.2-3.2, P=0.011) and patients receiving methylprednisolone during conditioning (HR 1.9, 95% CI 1.1-3.3, P=0.019 1), patients with cGvHD also having a higher risk for NRM (HR 13.2, 95% CI 1.2-143, P=0.03), as well as those receiving steroids for >3 months (HR 40.3, 95% CI 2.3-718, P=0.02) and those receiving antithymocyte globulin (HR 9.6, 95% CI 0.8-68, P=0.024). CONCLUSIONS: A significant proportion of long-term survivors of HSCT had late complications. cGvHD remained an important risk factor for late complications despite T-cell depletion resulting in immunosuppression and infectious complications.

[Endobronchic palliative brachytherapy]. / Brachythérapie endobronchique palliative.

Brachytherapy, the placement of an encapsuled radioactive source (Iridium) in or near a tumor, is a palliative therapeutic modality available for patients suffering of a bronchogenic cancer, especially if they present invalidating symptoms such an incoercible cough, haemoptysis, dyspnea. The treatment modality is indicated if chemotherapy or external irradiation are not possible. It is typically a team work.

Patterns of failure and outcome in patients with carcinoma of the anal margin.

BACKGROUND: To evaluate the outcome of patients with carcinoma of anal margin in terms of recurrence, survival, and radiation toxicity. METHODS: A series of 45 consecutive patients, with anal margin carcinoma treated between 1983 and 2006 with curative intent at two institutions, was retrospectively analyzed. A surgical excision (close or positive surgical margin in 22 out of 29 patients) was realized before radiotherapy (RT). RT consisted of definitive external beam RT (EBRT) in 36 patients, brachytherapy (BT) alone in two patients, and both BT and EBRT in seven patients. The median total radiation dose was 59.4 Gy (range, 30-74 Gy). RESULTS: The 5-year locoregional control (LRC) rate was 78% [95% confidence interval (CI), 64-93%]. The 5-year disease-specific survival (DSS) and overall survival (OS) rates were respectively 86% (95% CI, 72-99%) and 55% (95% CI, 44-66%). The overall anal conservation rate was 80% for the whole series. There was no significant association between local recurrence and patient age, histological grade, tumor size, T stage, overall treatment time, RT dose, or chemotherapy. Long-term side effects were observed in 15 patients (33%). Only three patients developed grade 3-4 late toxicity (CTCAE/NCI v3.0). Significant relationship was found between dose, and complication rate (48% for dose >or=59.4 Gy versus 8% for dose < 59.4 Gy; P = 0.03). CONCLUSIONS: We conclude that definitive RT and/or BT yield a good local control and disease-specific survival comparable with published data. This study suggests that radiation dose over 59.4 Gy seems to increase treatment-related morbidity.

[Renal artery stenosis after radiotherapy for Ewing's sarcoma]. / Radiotherapieinduzierte Nierenarterienstenose nach Behandlung eines Ewing-Sarkoms.

BACKGROUND: The fact that therapeutic irradiation can induce significant stenosis in the arteries of the head, neck, and chest, as well as in the aorta and the iliac arteries, is familiar in daily practice and well documented in the literature. By contrast, radiation-induced renal artery stenosis seems to be a less widely known complication. PATIENTS AND METHODS: The sudden onset of medically refractory arterial hypertension and coma in a 27-year-old man is reported, who had been treated at age 20 with chemotherapy and radiotherapy for Ewing's sarcoma in the lumbar region. This treatment had been performed at the hospital of Sion, Switzerland in 2001. Also, the relevant literature from 1965 to 2007 is reviewed to underscore various aspects of this problem and to demonstrate the clinical relevance of renal artery stenosis as a potential long-term sequela of radiotherapy. CONCLUSION: Radiation-induced renal artery stenosis has only rarely been described in the literature, but arterial hypertension due to radiation-induced renal artery stenosis is a serious long-term sequela that can appear at a latency of up to 20 years after treatment. The paucity of reports presumably reflects the lesser frequency of radiotherapy for retroperitoneal tumors as compared to head-and-neck cancers, as well as lower awareness of the problem due to diagnostic bias in the era before CT and MRI were in routine use: at that time, carotid artery stenosis was easy to diagnose by ultrasonography, while radiation-induced renal artery stenosis, whose real incidence may well be higher, probably often went undetected. Thus, when a patient with a history of abdominal or retroperitoneal radiotherapy unexpectedly develops intractable hypertension, radiation-induced renal artery stenosis must be included in the differential diagnosis.

Concomitant cisplatin significantly improves locoregional control in advanced head and neck cancers treated with hyperfractionated radiotherapy.

PURPOSE: To determine whether the application of two courses of cisplatin simultaneously with hyperfractionated radiotherapy improves the outcome in locally advanced and/or node-positive nonmetastatic carcinomas of the head and neck, compared with hyperfractionated radiotherapy alone. PATIENTS AND METHODS: From July 1994 to July 2000, 224 patients with squamous cell carcinomas of the head and neck (excluding nasopharynx and paranasal sinus) were randomly assigned to hyperfractionated radiotherapy (median dose, 74.4 Gy; 1.2 Gy twice daily) or the same radiotherapy combined with two cycles of concomitant cisplatin (20 mg/m2 on 5 days of weeks 1 and 5). The primary end point was time to any treatment failure; secondary end points were locoregional failure, metastatic relapse, overall survival, and late toxicity. RESULTS: There was no difference in radiotherapy between both treatment arms (74.4 Gy in 44 days). The full cisplatin dose was applied in 93% and 71% of patients during the first and second treatment cycles, respectively. Acute toxicity was similar in both arms. Median time to any treatment failure was not significantly different between treatment arms (19 months for combined treatment and 16 months for radiotherapy only, respectively) and the failure-free rate at 2.5 years was 45% and 33%, respectively. Locoregional control and distant disease-free survival were significantly improved with cisplatin (log-rank test, P = .039 and .011, respectively). The difference in overall survival did not reach significance (log-rank test, P = .147). Late toxicity was comparable in both treatment groups. CONCLUSION: The therapeutic index of hyperfractionated radiotherapy is improved by concomitant cisplatin.

Assessment of quality of life in patients with rectal cancer treated by preoperative radiotherapy: a longitudinal prospective study.

PURPOSE: To assess prospectively the quality of life (QOL) of patients treated by preoperative radiotherapy (RT) and surgery for locally advanced rectal cancer. METHODS AND MATERIALS: We studied 53 patients treated with bi-fractionated RT (50 Gy in 40 fractions within 4 weeks) followed at a median interval of 45 days by abdominoperineal resection in 11 patients and low anterior resection in 42 patients. Their QOL was assessed using two self-rating questionnaires developed by the European Organization for Research and Treatment of Cancer (EORTC): one was cancer specific (EORTC QLQ-C30) and one was site specific (EORTC QLQ-C38). The questionnaires were completed before RT and 12-16 months after RT, at which time 17 patients had undergone colostomy. We hypothesized that at least some scores of the various scales would vary between the two analyses. RESULTS: Compared with the pre-RT scores, at 1 year, patients reported statistically significant improvement in their emotional state (median 75 vs. 100, p <0.0001), perspective of the future (67 vs. 100, p = 0.0004), and their global QOL (75 vs. 83, p = 0.0008), as well as a decrease in GI symptoms (13 vs. 0, p = 0.002). However, the sexual dysfunction score increased significantly, particularly in men (17 vs. 83, p = 0.0045), and a trend toward a lower body image score was observed (100 vs. 89, p = 0.068). At 1 year, patients with colostomies reported similar or significantly improved symptom scores for fatigue, pain, GI problems, and sleep disturbance, but no such improvements were observed in patients without stomas. CONCLUSION: One year after combined treatment for locally advanced rectal cancer, patients exhibited statistically significant improvement in some important QOL outcomes, including global QOL, despite a decrease in sexual function and body image. Any additional improvement in QOL outcome may require refinements in the RT and surgical techniques to reduce late sequelae, particularly sexual dysfunction. Our results suggest that QOL considerations do not justify sphincter-conserving approaches if locoregional tumor control would be compromised.

Can concomitant-boost accelerated radiotherapy be adopted as routine treatment for head-and-neck cancers? A 10-year single-institution experience.

PURPOSE: Accelerated schedules are effective in overcoming repopulation during radiotherapy (RT) for head-and-neck cancers, but their feasibility is compromised by increased toxicity. The therapeutic ratio may be particularly favorable for 5-week regimens. This study reports the 10-year experience of a single institution in the routine use of concomitant boost RT as standard radical treatment in all but the most favorable stage patients. METHODS AND MATERIALS: Between February 1991 and June 2001, 296 patients (mean age, 59 years) were treated with concomitant boost RT either alone (67%) or combined with cisplatin-based chemotherapy (33%), with a median tumor dose of 69.9 Gy. Tumors were located in the oropharynx in 52%, hypopharynx in 20%, larynx in 15%, nasopharynx in 7%, and oral cavity in 6%. International Union Against Cancer Stage III-IV disease represented 77% of tumors. The median follow-up for surviving patients was 55 months (range, 10-138 months). RESULTS: The RT schedule was completed to the prescribed dose in all but 1 patient. Twenty patients (7%) had a treatment interruption (median, 5 days; range, 2-35 days). Grade 3-4 Radiation Therapy Oncology Group acute toxicity was observed in 77% of patients, and nutritional support was required in 110 patients (37%). For all patients, the 5-year actuarial locoregional control and disease-free survival rate was 72% and 61%, respectively. In a multivariate analysis, only T and N stage was significantly associated with locoregional control and disease-free survival. Grade 3-4 late toxicity occurred in 14%, mostly bone and cartilage necrosis. CONCLUSIONS: The present, moderately accelerated, concomitant boost regimen is logistically feasible, causing minimal inconvenience to the technical staff and yielding a high rate of patient compliance. Concomitant chemotherapy administration is feasible provided that patients are carefully selected and supportive care is introduced in a timely fashion. Considering the manageable toxicity and the satisfactory tumor control obtained, this regimen represents a good choice when considering implementation of an altered RT fractionation schedule as standard treatment for head-and-neck cancers.

Preoperative hyperfractionated radiotherapy for locally advanced rectal cancers: a phase I-II trial.

PURPOSE: To assess the toxicity, pathologic response rates, type of surgery, and oncologic results in a prospective Phase I-II trial using pure hyperfractionated radiotherapy (RT) preoperatively in locally advanced rectal cancer. METHODS AND MATERIALS: Between September 1997 and April 2000, 50 patients with T3-T4 or N1 rectal cancers were treated preoperatively with 50 Gy (45 Gy to the pelvis and a 5-Gy tumor boost) in 40 fractions of 1.25 Gy during 4 weeks. The pretreatment tumor stage as determined by CT and endorectal ultrasonography (80% of patients) included 1 Stage T2 (2%), 45 T3 (90%), and 4 T4 (8%). Nodal involvement (N1) was documented in 26 patients (52%). Surgery was performed at a median interval of 45 days (range 26-114 days) after RT completion. Seventeen patients who presented with pT4 or pN1 and/or pM1 received 5-fluorouracil-based chemotherapy postoperatively. RESULTS: All patients completed the RT schedule as planned. Severe acute toxicities included two Grade 3 skin reactions (4%) that did not require a break. The other acute toxicities were Grade 2 or less (skin, diarrhea, urinary, rectal tenesmus, and fatigue). A complete pathologic response was observed in 7 patients (14%), and microscopic residual cancer was found in 10 (20%). Of the 20 patients presenting with tumor located < or = 6 cm from the anal verge, sphincter-saving surgery was performed in 14 (70%). At 3 years, the actuarial locoregional control rate was 90.5%, and the disease-free survival rate was 74.6%. At a median follow-up of 32 months, 4 patients (8%) presented with severe late complications (Grade 3-4) that might have been RT related (one rectovaginal fistula, two chronic perineal fistulas, and one bilateral ureteral stenosis). CONCLUSION: In locally advanced rectal cancer, preoperative hyperfractionated RT to a total dose of 50 Gy is feasible, with acceptable acute and late toxicity and an objective downstaging effect. In view of these results, this schedule might be used as a basis for additional investigation regarding RT dose escalation or the addition of concomitant chemotherapy.

Renal insufficiency in patients with hematologic malignancies undergoing total body irradiation and bone marrow transplantation: a prospective assessment.

PURPOSE: Patients with malignant hematologic disorders undergoing bone marrow transplantation (BMT) may develop renal insufficiency. A study was undertaken to assess prospectively the subclinical renal function changes with radioisotopic methods in patients undergoing BMT for hematologic malignancies. METHODS AND MATERIALS: We studied 71 patients with normal renal function undergoing BMT for various hematologic malignancies, mostly leukemias. Conditioning included chemotherapy and 12 Gy (45 patients) or 13.5 Gy (26 patients) fractionated total-body irradiation (TBI). In 21 patients receiving 12 Gy TBI, the kidney dose was limited to 10 Gy using partial transmission blocks fabricated after renal opacification with nonionic, hypo-osmolar contrast medium. The glomerular filtration rate (GFR) and effective renal plasmatic flow (ERPF) were determined radioisotopically before conditioning and at 4, 12, and 18 months, using (51)Cr ethylene-diamine-tetra-acetic acid and (131)I ortho-iodo-hippurate, respectively. Renal insufficiency was defined as a decrease of >/=30% in GFR or ERPF compared with the baseline values. The potential influence of patient- and treatment-related variables on renal dysfunction was assessed. RESULTS: At 4 (early) and 12-18 (late) months, a >/=30% GFR drop was observed in 54% and 49% of patients and a >/=30% ERPF drop in 44% and 34% of patients, respectively. After stepwise logistic analysis, a GFR reduction at 4 months correlated significantly with age (<40 years old, worse), TBI using kidney blocks (partial kidney shielding to 10 Gy was associated with a higher rate of renal dysfunction at 4 months compared with the full TBI dose), and days of aminoglycoside/vancomycin use. An ERPF drop at 4 months was independently related with the days of amphotericin use and days of prostaglandin E(1) use (prophylaxis against hepatic venoocclusive disease). A GFR and ERPF reduction at 12-18 months correlated with days of amphotericin use and days of prostaglandin E(1) use, respectively. CONCLUSION: Early post-BMT renal dysfunction is associated with the administration of potentially nephrotoxic drugs. An inverse correlation with the prescribed TBI dose was observed; patients whose kidneys received 10 Gy through the use of partial shielding blocks had significantly greater renal dysfunction at 4 months. The administration of potentially nephrotoxic contrast agents used in radiotherapy treatment planning may be responsible for the latter observation. Prostaglandin E(1) use correlated with a significant reduction in ERPF at both 4 and 12-18 months.

Outcome and patterns of failure in testicular lymphoma: a multicenter Rare Cancer Network study.

PURPOSE: To assess the outcome and patterns of failure in patients with testicular lymphoma treated by chemotherapy (CT) and/or radiation therapy (RT). METHODS AND MATERIALS: Data from a series of 36 adult patients with Ann Arbor Stage I (n = 21), II (n = 9), III (n = 3), or IV (n = 3) primary testicular lymphoma, consecutively treated between 1980 and 1999, were collected in a retrospective multicenter study by the Rare Cancer Network. Median age was 64 years (range: 21-91 years). Full staging workup (chest X-ray, testicular ultrasound, abdominal ultrasound, and/or thoracoabdominal computer tomography, bone marrow assessment, full blood count, lactate dehydrogenase, and cerebrospinal fluid evaluation) was completed in 18 (50%) patients. All but one patient underwent orchidectomy, and spermatic cord infiltration was found in 9 patients. Most patients (n = 29) had CT, consisting in most cases of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with (n = 17) or without intrathecal CT. External RT was delivered to scrotum alone (n = 12) or testicular, iliac, and para-aortic regions (n = 8). The median RT dose was 31 Gy (range: 20-44 Gy) in a median of 17 fractions (10-24), using a median of 1.8 Gy (range: 1.5-2.5 Gy) per fraction. The median follow-up period was 42 months (range: 6-138 months). RESULTS: After a median period of 11 months (range: 1-76 months), 14 patients presented lymphoma progression, mostly in the central nervous system (CNS) (n = 8). Among the 17 patients who received intrathecal CT, 4 had a CNS relapse (p = NS). No testicular, iliac, or para-aortic relapse was observed in patients receiving RT to these regions. The 5-year overall, lymphoma-specific, and disease-free survival was 47%, 66%, and 43%, respectively. In univariate analyses, statistically significant factors favorably influencing the outcome were early-stage and combined modality treatment. Neither RT technique nor total dose influenced the outcome. Multivariate analysis revealed that the most favorable independent factors predicting the outcome were younger age, early-stage disease, and combined modality treatment. CONCLUSIONS: In this multicenter retrospective study, CNS was found to be the principal site of relapse, and no extra-CNS lymphoma progression was observed in the irradiated volumes. More effective CNS prophylaxis, including combined modalities, should be prospectively explored in this uncommon site of extranodal lymphoma.

Elective inguinal node irradiation in early-stage T2N0 anal cancer: prognostic impact on locoregional control.

PURPOSE: To evaluate the influence of elective inguinal node radiation therapy (INRT) on locoregional control (LRC) in patients with early-stage T2N0 anal cancer treated conservatively with primary RT. METHODS AND MATERIALS: Between 1976 and 2008, 116 patients with T2 node-negative anal cancer were treated curatively with RT alone (n=48) or by combined chemoradiation therapy (CRT) (n=68) incorporating mitomycin C and 5-fluorouracil. Sixty-four percent of the patients (n=74) received elective INRT. RESULTS: Over a median follow-up of 69 months (range, 4-243 months), 97 (84%) and 95 patients (82%) were locally and locoregionally controlled, respectively. Rates for 5-year actuarial local control, LRC, cancer-specific, and overall survival for the entire population were 81.7% ± 3.8%, 79.2% ± 4.1%, 91.1% ± 3.0%, and 72.1% ± 4.5%, respectively. The overall 5-year inguinal relapse-free survival was 92.3% ± 2.9%. Isolated inguinal recurrence occurred in 2 patients (4.7%) treated without INRT, whereas no groin relapse was observed in those treated with INRT. The 5-year LRC rates for patients treated with and without INRT and with RT alone versus combined CRT were 80.1% ± 5.0% versus 77.8% ± 7.0% (P=.967) and 71.0% ± 7.2% versus 85.4% ± 4.5% (P=.147), respectively. A trend toward a higher rate of grade ≥3 acute toxicity was observed in patients treated with INRT (53% vs 31%, P=.076). CONCLUSIONS: In cases of node-negative T2 anal cancer, the inguinal relapse rate remains relatively low with or without INRT. The role of INRT in the treatment of early-stage anal carcinoma needs to be investigated in future prospective trials.

Sequential or concomitant chemotherapy in limited stage small-cell lung cancer.

PURPOSE: Chemotherapy (CT) combined with radiation therapy (RT) is the standard treatment for limited disease small-cell lung cancer (LDSCLC). Many questions including RT dose, fractionation, and sequence of RT/CT administration remain controversial. In this paper, we retrospectively assessed the outcome of patients with LDSCLC treated with radiation of at least 50 Gy. METHODS AND MATERIALS: From December 1997 to January 2006, 69 consecutive patients with LDSCLC were treated at our institutions. Treatment consisted of at least 4 cycles of CT, and 3D conformal thoracic RT. The median age was 61 years (range, 37-78 years). Sequential or concomitant CT/RT was given in 47 (68%) and 22 (32%) of the patients, respectively. The median RT dose was 60 Gy. Prophylactic cranial irradiation (PCI) was administered in 47 (68%) patients. RESULTS: With a median follow-up of 36 months (range, 6-107), 16 patients were alive without disease. The median overall survival time was 24 months, with a 3-year survival rate of 29%. The 3-year disease-free survival (DFS) and loco-regional control (LRC) rates were 23% and 60%, respectively. A better DFS was significantly associated with performance status (PS) 0 (p = 0.004), complete response to treatment (p = 0.03), and PCI group (p = 0.03). A trend towards improved overall survival (OS) was observed for patients who underwent PCI (p = 0.07). Patients treated with sequential CT/RT had a better outcome than those treated with concomitant treatment (3-year DFS rate 27% vs. 13%; p = 0.04). However, PCI was delivered more frequently for the sequential group. No significant dose-response relationship was found in terms of LRC. The multivariate analysis showed that complete response to treatment was the only significant factor for OS. CONCLUSION: Complete response to treatment was the most important factor for OS. A better DFS was significantly associated with the PCI group. We did not find a significant difference in outcome between patients receiving doses of 60 Gy or more and patients receiving 60 Gy or less.

Whole brain radiotherapy with a conformational external beam radiation boost for lung cancer patients with 1-3 brain metastasis: a multi institutional study.

BACKGROUND: To determine the outcome of patients with brain metastasis (BM) from lung cancer treated with an external beam radiotherapy boost (RTB) after whole brain radiotherapy (WBRT). METHODS: A total of 53 BM patients with lung cancer were treated sequentially with WBRT and RTB between 1996 and 2008 according to our institutional protocol. Mean age was 58.8 years. The median KPS was 90. Median recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) grouping were 2 and 2.5, respectively. Surgery was performed on 38 (71%) patients. The median number of BM was 1 (range, 1-3). Median WBRT and RTB combined dose was 39 Gy (range, 37.5-54). Median follow-up was 12.0 months. RESULTS: During the period of follow-up, 37 (70%) patients died. The median overall survival (OS) was 14.5 months. Only 13 patients failed in the brain. The majority of patients (n = 29) failed distantly. The 1-year OS, -local control, extracranial failure rates were 61.2%, 75.2% and 60.8%, respectively. On univariate analysis, improved OS was found to be significantly associated with total dose (< or = 39 Gy vs. > 39 Gy; p < 0.01), age < 65 (p < 0.01), absence of extracranial metastasis (p < 0.01), GPA > or = 2.5 (p = 0.01), KPS > or = 90 (p = 0.01), and RPA < 2 (p = 0.04). On multivariate analysis, total dose (p < 0.01) and the absence of extracranial metastasis (p = 0.03) retained statistical significance. CONCLUSIONS: The majority of lung cancer patients treated with WBRT and RTB progressed extracranially. There might be a subgroup of younger patients with good performance status and no extracranial disease who may benefit from dose escalation after WBRT to the metastatic site.

Hypofractionated boost with high-dose-rate brachytherapy and open magnetic resonance imaging-guided implants for locally aggressive prostate cancer: a sequential dose-escalation pilot study.

PURPOSE: To evaluate the feasibility, tolerance, and preliminary outcome of an open MRI-guided prostate partial-volume high-dose-rate brachytherapy (HDR-BT) schedule in a group of selected patients with nonmetastatic, locally aggressive prostatic tumors. METHODS AND MATERIALS: After conventional fractionated three-dimensional conformal external radiotherapy to 64-64.4 Gy, 77 patients with nonmetastatic, locally aggressive (e.g., perineural invasion and/or Gleason score 8-10) prostate cancer were treated from June 2000 to August 2004, with HDR-BT using temporary open MRI-guided (192)Ir implants, to escalate the dose in the boost region. Nineteen, 21, and 37 patients were sequentially treated with 2 fractions of 6 Gy, 7 Gy, and 8 Gy each, respectively. Neoadjuvant androgen deprivation was given to 62 patients for 6-24 months. Acute and late toxicity were scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring system. RESULTS: All 77 patients completed treatment as planned. Only 2 patients presented with Grade > or =3 acute urinary toxicity. The 3-year probability of Grade > or =2 late urinary and low gastrointestinal toxicity-free survival was 91.4% +/- 3.4% and 94.4% +/- 2.7%, respectively. Rates of 3-year biochemical disease-free survival (bDFS) and disease-specific survival were 87.1% +/- 4.1% and 100%, respectively. CONCLUSIONS: Boosting a partial volume of the prostate with hypofractionated HDR-BT for aggressive prostate cancer was feasible and showed limited long-term toxicity, which compared favorably with other dose-escalation methods in the literature. Preliminary bDFS was encouraging if one considers the negatively selected population of high-risk patients in this study.

Preoperative concomitant hyperfractionated radiotherapy and gemcitabine for locally advanced rectal cancers: a phase I-II trial.

PURPOSE: The purpose of this study was to determine the maximum tolerated dose of gemcitabine when it was administered concomitantly with hyperfractionated radiotherapy before surgery in patients with locally advanced rectal cancers and to investigate the midterm efficacy of such a regimen. PATIENTS AND METHODS: Thirty-seven patients with stage II-III tumors as assessed by computed tomography/echoendoscopy were enrolled. Radiotherapy consisted of 50 Gy given in two daily fractions of 1.25 Gy over 4 weeks. The starting dose of gemcitabine was 10 mg/m(2)/day (in a 30-minute i.v. perfusion) twice weekly with planned escalation steps of 5 mg/m(2)/day. Surgery was planned at 6 weeks after the end of radiotherapy. Main end-points of the study were complete pathological tumor response, the rate of clear margin resection, and actuarial locoregional control and disease-free survival. The median follow-up for all patients was 32 months (range: 10-51 months). RESULTS: At the level of 45 mg/m(2), two of four patients presented with dose-limiting rectal toxicities (severe acute proctitis requiring hospitalization in the immediate postradiotherapy period). Thus, the gemcitabine biweekly dose of 40 mg/m(2) was considered to be the maximum tolerated dose. Among the 36 patients who underwent surgery, 17 (47%) had a marked pathological response, including six patients (17%) with a microscopically complete response and 11 (30%) with only microscopically residual carcinoma of less than 1 cm. All of them had clear surgical margins. At 3 years, actuarial overall survival rate was 85%, locoregional control was 94.5%, and disease-free survival was 67%. DISCUSSION: The present study determined the recommended dose of gemcitabine to be 40 mg/m(2) when administered concurrently twice a week with 50 Gy hyperfractionated radiotherapy for the preoperative treatment of locally advanced rectal cancers. The encouraging pathological response rate and the very low locoregional recurrence rate suggest that this innovative approach merits further investigation.

Early morbidity after radiotherapy with or without chemotherapy in advanced head and neck cancer. Experience from four nonrandomized studies.

BACKGROUND: Data on early treatment-related morbidity after radiotherapy alone (RT; 217 patients) or combined with chemotherapy (RT + CT; 182 patients) of head and neck squamous cell carcinoma are analyzed. PATIENTS AND METHODS: The patients were treated between November 1985 and November 1996 in four Swiss centers that independently introduced combined-modality therapy in selected cases of head and neck cancer. RT schedules varied among the four centers, but within each institution all patients received the same dose-fractionation schedule irrespective of whether they had CT or not. The following early morbidity items were evaluated: skin, mucosa, larynx, salivary glands, dysphagia, weight loss, and toxic death. Toxicity was scored using the EORTC/RTOG scale. RESULTS: Although considerable variation was noted among the treatment schedules/centers, the main findings are as follows: (1) early morbidity was significantly enhanced after all five RT + CT schedules compared with RT alone; (2) typically, a third of the patients lost > 10% of their body weight during concurrent RT + CT as compared with 10% of the patients receiving RT alone; (3) at 12 weeks, the prevalence of grade 2 morbidity was 25-60% after RT + CT as compared with 4-20% after RT alone. CONCLUSION: A number of early morbidity items were found to be more prevalent and/or more severe after RT + CT than after RT alone.