Early pulmonary toxicity following lung stereotactic body radiation therapy delivered in consecutive daily fractions

Background and purpose

Identify the incidence of early pulmonary toxicity in a cohort of patients treated with lung stereotactic body radiation therapy (SBRT) on consecutive treatment days.

Material and methods

A total of 88 lesions in 84 patients were treated with SBRT in consecutive daily fractions (Fx) for medically inoperable non-small cell lung cancer or metastasis. The incidence of pneumonitis was evaluated and graded according to the NCI CTCAE v3.0.

Results

With a median follow-up of 15.8 months (range 2.5-28.6), the median age at SBRT was 71.8 years (range 23.8-87.8). 47 lesions were centrally located and 41 were peripheral. Most central lesions were treated with 48 Gy in 4 Fx, and most peripheral lesions with 54 Gy in 3 Fx. The incidence of grade ?2 pneumonitis was 12.5% in all patients treated, and 14.3% among the subset of patients treated with 54 Gy in 3 Fx. A total of two grade 3 toxicities were seen as one grade 5 toxicity in a patient treated for recurrence after pneumonectomy.

Conclusions

Treating both central and peripheral lung lesions with SBRT in consecutive daily fractions in this cohort was well tolerated and did not cause excessive early pulmonary toxicity.     

Time course of hypothalamic-pituitary deficiency in adults receiving cranial radiotherapy for primary extrasellar brain tumors

Background

No longitudinal data on hypothalamic-pituitary (HP) function are available in patients who had received cranial radiation therapy (CRT) for primary extrasellar brain tumors (PBT).

Purpose

To investigate the effects of CRT on HP function in adults with PBT.

Patients and methods

Twenty-six adults irradiated for PBT and six CRT naive controls were studied. CRT was delivered with 6 MV X-ray by a linear accelerator (2 Gy fraction schedule). Gross Tumor Volume (GTV) excluded the HP region that was contoured on the planning CT. Median dose to the HP region was 41.8 Gy (IQR: 30.7-49.8).

Results

All controls maintained normal HP function. Hypopituitarism developed in 38% of CRT patients (GH deficiency 29%, ACTH 22%, TSH 14%, gonadotropin 4%, no abnormal prolactin level or diabetes insipidus). All HP failures occurred within 32 months after CRT.

Conclusions

Adults undergoing CRT for PBT are at increased risk for HP dysfunction within 3 years from CRT. Endocrine surveillance is recommended also in adults patients exposed to CRT for primary brain tumors distant from HP region.     

Stereotactic fractionated radiotherapy for Klatskin tumours

Background and purpose

In spite of various efforts perihilar cholangiocellular carcinoma (Klatskin tumour) has still a bad prognosis. The treatment of patients with inoperable Klatskin tumours by stereotactic fractionated radiotherapy (SFRT) was analysed retrospectively.

Patients, methods and materials

In our department 13 patients were treated for Klatskin tumours by SFRT (32-56 Gy, 3 × 4 Gy/week) from 1998 to 2008. The treatment technique was developed from stereotactic body frame radiotherapy to image guided (IGRT) stereotactic radiotherapy with control of patient positioning by cone beam computer tomography (CBCT). 6/13 patients received additional chemotherapy before or after SFRT.

Results

A median survival of 33.5 (6.6-60.4) months after diagnosis was reached by SFRT. The median time of freedom from tumour progression was 32.5 (6.1-60.4, last patient died without tumour progression) months. The therapy was tolerated very well. Nausea was the most common side effect. 5/13 patients suffered from recurrent cholangitis caused and enhanced by the primary tumour and drainages or stents in the bile ducts.

Conclusions

In the context of reaching local control being still the main problem of Klatskin tumour patients, SFRT seems to be a very promising method for the treatment of these tumours.     

Repeated linac-based radiosurgery in high-grade cerebral arteriovenous-malformations (AVM) Spetzler-Martin grade III to IV previously treated with radiosurgery

Background

Aim was to access outcome and toxicity of repeated linac-based radiosurgery in incompletely obliterated cerebral AVM.

Patients and methods

Between 1998 and 2008, 11 patients were treated with repeated radiosurgery. The median dose to the 80%-isodose was 15 Gy (range, 12-18 Gy). During initial radiosurgery the median dose was 18 Gy (range, 9-22 Gy).

Results

The median time interval between initial radiosurgery and re-treatment was 9 years (range, 4-16 years). The median follow-up was 26 months (range, 2-115 months). Treatment response was seen in 8 patients (89%). Complete (partial) obliteration was achieved in 5 (3) patients (56%, 33%, respectively).The median time to complete obliteration was 26 months (range, 5-45 months). Pre-existing neurological symptoms improved in 2 patients (18%), were stable in 7 patients (64%) and worsened in 2 patients (18%). Prevalence of intracranial hemorrhage was 9% (1/11). Post-re-treatment intracranial hemorrhage rate was 2.7% (1/38 years at risk). During follow-up, no secondary malignancies or toxicity > grade III were observed.

Conclusion

Repeated linac-based radiosurgery in incompletely obliterated cerebral AVM is an effective treatment option with a high rate of treatment response and an acceptable risk for side effects. Marginal doses above 15 Gy might further improve the rate of complete obliterations.     

Multicenter observational study of erlotinib therapy (OBSTAR) for non small-cell lung cancer: a GFPC study

Context

Erlotinib therapy for non small-cell lung cancer (NSCLC) has mainly been evaluated in randomized trials.

Method

OBSTAR was a multicenter, retrospective, observational study involving all patients treated with erlotinib in 18 French centers between June 2005 and September 2007. The analyses focused on the patients’ characteristics, previous treatments, and treatment efficacy during a three-year follow-up period.

Results

534 patients were included in this study. The median survival times were respectively 5.2 [3.7-7.4] and 4.7 [4.1-5.7] months, depending to whether erlotinib was used as second- (n = 190), or ≥third-line treatment (n = 305). The disease control rate were 39.1% [30.2-48.7] and 29.9% [29.6-36.9] according to the line of treatment. Factors predictive of an objective response were gender, age, and smoking status. Factors predictive of progression were age, sex, smoking status, the line of treatment, and the number of metastases. Treatment had to be interrupted for toxicity in 8.5% of cases.

Conclusion

This study of erlotinib therapy in 2005-2007 confirms, in the general NSCLC patient population, the results of pivotal trials.     

Lymph node growth rate in testicular germ cell tumours: implications for computed tomography surveillance frequency

Aim

To estimate the growth rate of lymph nodes in patients on surveillance for testicular cancer who developed recurrent disease.

Materials and methods

During a 7-year period, 318 patients at our institution were managed by surveillance and 39 relapsed (12.3%). The computed tomography scans of 28 patients (median age 32 years; range 19-51 years) who met our inclusion criteria and who developed recurrent disease in the abdomen/pelvis were retrospectively reviewed. Thirteen patients had non-seminoma and 15 had seminoma. To estimate the lymph node growth rate, the slope of lymph node size over time was calculated.

Results

The median length of time from orchiectomy to the recurrence computed tomography was 131 days (range 49-520) or about 4.4 months for non-seminoma patients and 373 days (range 129-675) or about 12.3 months for seminoma patients. The median size of the involved lymph node at final computed tomography for seminoma patients was 12 mm (range 9-31 mm) and for non-seminoma patients was 15 mm (range 10-56 mm). The median lymph node growth rate for patients with seminoma was 1.35 mm/month (range 0.62-4.56) and for patients with non-seminoma 2.99 mm/month (range 0.77-7.06); the difference in growth rates was statistically significant (P = 0.029).

Conclusions

There is a statistically significant faster growth rate of lymph nodes in patients with recurrent non-seminoma compared with patients with seminoma. This finding supports a more frequent computed tomography schedule during the first 2 years of surveillance in non-seminoma patients compared with seminoma patients.     

Robotic system-based fractionated stereotactic radiotherapy in locally recurrent nasopharyngeal carcinoma

Purpose

We reviewed survival, local control, and toxicity in patients with locally recurrent nasopharyngeal carcinoma (NPC) who had been treated with fractionated stereotactic radiotherapy (FSRT).

Materials and methods

Between June 2002 and March 2008, we retrospectively reviewed 35 patients with locally recurrent NPC treated using FSRT with CyberKnife. Gross tumor volumes ranged from 2.6 to 64.0 ml (median, 7.9 ml). Radiation doses were prescribed at the isodose line (75-84% of the maximum dose; median, 80%). The prescribed dose of FSRT ranged from 24 to 45 Gy (median, 33 Gy) in three or five fractions.

Results

The overall survival (OS) rate, local failure-free survival (LFFS) rate, and disease progression-free survival (DPFS) rate at 5 years were 60%, 79%, and 74%, respectively. Twenty-three patients achieved complete response after FSRT. Only T stage at recurrence was an independent prognostic factor for OS and DPFS. Five patients exhibited severe late toxicity (Grade 4 or 5).

Conclusions

With regard to OS and LFFS, our study provided favorable outcomes. The incidence of severe late toxicities was acceptable in our study. FSRT would be considered as the alternative treatment of choice in re-irradiation for locally recurrent NPC.     

Treatment with curative intent of stage III non-small cell lung cancer patients of 75 years: a prospective population-based study

Background

There is little data on the survival of elderly patients with stage III non-small cell lung cancer (NSCLC).

Methods

Patients with stage III NSCLC in the Netherlands Cancer Registry/Limburg from January 1, 2002 to December 31, 2008 were included.

Findings

One thousand and two patients with stage III were diagnosed, of which 237 were 75 years or older. From 228 patients, co-morbidity scores were available. Only 33/237 patients (14.5%) had no co-morbidities, 195 (85.5%) had one or more important co-morbidities, 60 (26.3%) two or more co-morbidities, 18 (7.9%) three or more co-morbidities and 2 patients (0.9%) suffered from four co-morbidities. Forty-eight percent were treated with curative intent. No significant difference in Charlson co-morbidity, age or gender was found between patients receiving curative or palliative intent treatment. Treatment with curative intent was associated with increased overall survival (OS) compared to palliative treatment: median OS 14.2 months (9.6-18.7) versus 5.2 months (4.3-6.0), 2-year OS 35.5% versus 12.1%, for curative versus palliative treatment.Patients who received only radiotherapy with curative intent had a median OS of 11.1 months (95% confidence interval [95% CI] 6.4-15.8) and a 5-year OS of 20.3%; for sequential chemotherapy and radiotherapy, the median OS was 18.0 months (95% CI 12.2-23.7), with a 5-year OS of 14.9%. Only four patients received concurrent chemo-radiation.

Interpretation

In this prospective series treating elderly patients with stage III NSCLC with curative intent was associated with significant 5-year survival rates.     

Long-term outcome of high-precision radiotherapy in patients with brain stem gliomas: Results from a difficult-to-treat patient population using fractionated stereotactic radiotherapy

Introduction

To assess long-term outcome in 85 patients with brain stem gliomas treated with fractionated stereotactic radiation therapy (FSRT).

Patient and methods

Thirty-nine patients were females, and 46 were males. Median age at primary diagnosis was 26 years. Thirty-one patients were younger than 18 years. Histopathological examination confirmed a low-grade glioma in 57 patients. Of the group of high-grade gliomas, six were anaplastic astrocytomas, and two were classified as glioblastoma.Radiation therapy was performed as FSRT. The median target volume was 101 ml. We applied a median dose of 54 Gy in conventional fractionation of 1.8 Gy. In seven of 85 patients (8%) FSRT was performed as re-irradiation.

Results

The median follow-up time was 42 months. Median overall survival (OS) was 81 months. OS rates were 77% at 12 months, 70% at 24 months, and 63% at 36 months. Significant impact on OS could be shown for pilocytic histology, age, neurosurgical resection as well as for the presence of cyst on MR-imaging.Median progression-free survival (PFS) after FSRT was 52 months. PFS rates at 12 months were 70%, and 63% and 58% at 24 and 36 months, respectively.Histology, partial neurosurgical resection and the duration of symptoms could be identified as significant prognostic factors.

Conclusion

Long-term outcome of FSRT in patients with brain stem gliomas is acceptable with low rates of side effects. Significant impact on outcome could be shown for histology, age, extent of neurosurgical resection as well as for cyst formation. No dose-response relationship could be observed.     

Durable palliation of breast cancer chest wall recurrence with radiation therapy, hyperthermia, and chemotherapy

Background and purpose

Chest wall recurrences of breast cancer are a therapeutic challenge and durable local control is difficult to achieve. Our objective was to determine the local progression free survival (LPFS) and toxicity of thermochemoradiotherapy (ThChRT) for chest wall recurrence.

Methods

Twenty-seven patients received ThChRT for chest wall failure from 2/1995 to 6/2007 and make up this retrospective series. All received concurrent superficial hyperthermia twice weekly (median 8 sessions), chemotherapy (capecitabine in 21, vinorelbine in 2, and paclitaxel in 4), and radiation (median 45 Gy). Patients were followed up every 1.5-3 months and responses were graded with RECIST criteria and toxicities with the NCI CTC v4.0.

Results

Twenty-three (85%) patients were previously irradiated (median 60.4 Gy) and 22 (81%) patients received prior chemotherapy. Median follow-up was 11 months. Complete response (CR) was achieved in 16/20 (80%) of patients with follow-up data, and 1 year LPFS was 76%. Overall survival was 23 months for patients with CR, and 5.4 months in patients achieving a partial response (PR) (p = 0.01). Twenty-two patients experienced acute grade 1/2 treatment related toxicities, primarily moist desquamation. Two patients experienced 3rd degree burns; all resolved with conservative measures.

Conclusions

ThChRT offers durable palliation and prolonged LPFS with tolerable acute toxicity, especially if CR is achieved.     

Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: Safety profile for RTOG 0933

Background and purpose

RTOG 0933 is a phase II clinical trial of hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) to prevent radiation-induced neurocognitive decline. By quantifying baseline incidence of perihippocampal or hippocampal metastasis, we sought to estimate the risk of developing metastases in the hippocampal avoidance region (the hippocampus plus 5 mm margin).

Materials/methods

Patients with ?10 brain metastases treated at two separate institutions were reviewed. Axial images from pre-treatment, post-contrast MRIs were used to contour each metastasis and hippocampus according to a published protocol. Clinical and radiographic variables were correlated with perihippocampal metastasis using a binary logistical regression analysis, with two-sided p < 0.05 for statistical significance.

Results

1133 metastases were identified in 371 patients. Metastases within 5 mm of the hippocampus were observed in 8.6% of patients (95% CI 5.7-11.5%) and 3.0% of brain metastases. None of the metastases lay within the hippocampus. A 1-cm³ increase in the aggregate volume of intra-cranial metastatic disease was associated with an odds ratio of 1.02 (95% CI 1.006-1.034, p = 0.003) for the presence of perihippocampal metastasis.

Conclusion

With an estimated perihippocampal metastasis risk of 8.6%, we deem HA-WBRT safe for clinical testing in patients with brain metastases as part of RTOG 0933.     

A randomised phase II study of docetaxel/oxaliplatin and docetaxel in patients with previously treated non-small cell lung cancer: an Alpe-Adria Thoracic Oncology Multidisciplinary group trial (ATOM 019)

Introduction

To date, no combination regimen has proven superior to single agent chemotherapy as a second-line treatment for non-small cell lung cancer (NSCLC).

Methods

This multicenter, non-comparative randomised phase II trial evaluated the activity of docetaxel (75 mg/m² on day 1) with oxaliplatin (70 mg/m² on day 2) every 3 weeks in previously treated NSCLC patients; the reference arm was single-agent docetaxel (75 mg/m² on day 1 every 3 weeks). It was designed as a one-stage, three-outcome phase II trial; 21 evaluable patients were required in each arm. The primary end-point was response rate; secondary end-points were toxicity, progression free survival (PFS) and overall survival.

Results

Fifty patients were enrolled. Patient characteristics included male/female, 76/24%; median age 62 years; ECOG PS 0/1, 36/64%; previous platinum-based chemotherapy, 98%. Partial response was seen in 20% and 8%, stable disease in 52% and 32%, of patients treated with docetaxel/oxaliplatin and docetaxel, respectively. Main grade 3-4 toxicities were neutropenia 56% and 64%; febrile neutropenia 4% and 8%; diarrhoea 12% and 4% for docetaxel/oxaliplatin and docetaxel, respectively. Median PFS was 5.0 and 1.7 months, median survival 11.0 and 7.1 months, and 1-year survival 44% and 32% for docetaxel/oxaliplatin and docetaxel, respectively.

Conclusions

The study met its pre-defined study end-point; docetaxel/oxaliplatin and more generally platinum-containing doublets warrant further evaluation as second-line therapy for patients with NSCLC.     

Curative chemoradiotherapy for isolated retroperitoneal lymph node recurrence of colorectal cancer

Purpose

To investigate the efficacy of curative chemoradiotherapy for isolated retroperitoneal lymph node recurrence of colorectal cancer.

Materials and methods

Twenty-two colorectal cancer patients who received three-dimensional conformal radiotherapy (n = 20) or helical tomotherapy (n = 2) for isolated retroperitoneal lymph node recurrence were analyzed retrospectively. Radiation dose was 55.8 Gy in 31 fractions or 63 Gy in 35 fractions, and 60 Gy in 20 fractions by helical tomotherapy. All patients received concurrent chemotherapy and 16 (72.7%) received adjuvant chemotherapy.

Results

The treatment response was complete in 13 (59.1%), partial in 6 (27.3%), and stable in 3 (13.6%) patients. Median follow-up for 11 (50%) surviving patients was 32 months (range, 27-61). The 3- and 5-year overall survival rates were 64.7% and 36.4%, and median overall survival was 41 months. Recurrences developed in 15 (68.2%) patients; outside the retroperitoneum in 13. The 3- and 5-year recurrence-free survival rates were 34.1% and 25.6%, and median recurrence-free survival was 20 months. Response and adjuvant chemotherapy were significant prognostic factors for overall survival. Gastrointestinal toxicity ? Grade 3 was not observed.

Conclusions

Definitive chemoradiotherapy is an effective salvage treatment for isolated retroperitoneal lymph node recurrence of colorectal cancer without severe complications.     

Prophylactic irradiation of intervention sites in malignant pleural mesothelioma

Background and purpose

To assess the effectiveness of prophylactic irradiation of intervention track (PIT) to prevent tumor seeding in patients with malignant pleural mesothelioma.

Materials and methods

A retrospective review was conducted of 171 patients with a histological diagnosis of pleural mesothelioma with some undergoing prophylactic irradiation of intervention sites.

Results

Forty-eight patients (28%) received PIT. A majority of patients were followed until death. Thoracoscopy (88%) was the procedure most often performed. Thirty-three percent of patients received chemotherapy. The median dose of PIT was 21 Gy in 3 fractions with electrons or 6 MV photons. The local progression free survival (LPFS) at the intervention site was significantly higher in the PIT group and was not influenced by chemotherapy. At 6 months, LPFS for the intervention sites was 91% with PIT and 74% without PIT (p = 0.002). During the follow-up, 6 patients (13%) in the PIT group had tumor invasion of the subcutaneous tissue compared to 40 patients (33%) in the group without PIT (p = 0.008).

Conclusions

This study suggests that PIT in mesothelioma reduces the incidence of procedure tract metastasis. Finally, chemotherapy does not seem to have an influence on the incidence of tract metastasis.     

Small cell carcinoma of the upper urinary tract (UUT-SCC): report of a rare entity and systematic review of the literature

Background

Primary small cell carcinoma of the upper urinary tract (UUT-SCC) is an extremely uncommon disease. The current knowledge of these rare tumors is mainly based on case reports or small series.

Methods

We reported two cases and performed a systematic literature search from 1970 to 2010 for articles on UUT-SCC. Overall, 40 patients with UUT-SCC were reviewed, a database was generated to analyze clinical characteristics, pathological features and therapy outcomes and to attempt in identifying prognostic factors.

Results

For the 39 cases with available data, median age was 66.5 years and male-female ratio was 2:1. An Asian ethnic background was more common (59%). Surgery was the standard treatment given to all patients. In 67% of cases, SCC coexisted with another malignant component, including urothelial carcinoma in 62% of patients. Overall median survival was 15 months and the 1-, 2- and 3-year survival rates were 58.4%, 38.1% and 23.8%, respectively. Of all cases, 53.8% developed detectable metastasis in a median delay of 13 months. Pathological stage was the only significant prognostic factor found (p = 0.01). Patients who received adjuvant chemotherapy seem to have a higher median survival comparatively to those who did not receive chemotherapy but this was not statistically significant (24 vs. 12 months, p = 0.56).

Conclusions

UUT-SCC is an extremely rare tumor characterized by an aggressive clinical course. Local or distant metastases are frequent and survival is poor. Pathological stage appeared to be a prognostic factor for overall survival.     

Under usage of zoledronic acid in non-small cell lung cancer patients with metastatic bone disease--a short communication

Background and aim

The use of zoledronic acid (ZA) is now recommended for patients with NSCLC and metastatic bone disease (MBD). We thus examined the rates of ZA administration in NSCLC looking specifically at the use of this drug with systemic chemotherapy (ZCt) and comparing overall survival between patients who had ZCt from diagnosis to those who had chemotherapy (Ct) alone.

Method

In this retrospective audit, we analysed the data of 114 consecutive patients with stage IV NSCLC and MBD at presentation. Forty-three of these patients had received zoledronic acid and chemotherapy (ZCt) and 71 had received chemotherapy alone (Ct).

Results

Forty-three (37.7%, 43/114) of NSCLC patients diagnosed with MBD received ZA with their first chemotherapy (ZCt). Patients on ZCt, after adjustment for the planned prognostic factors (sites of disease, histology and PS), had better overall survival (OS), with a median of 34 weeks, compared to those who received chemotherapy alone, who had a median of 19 weeks (p = 0.03), HR = 0.60 (95%CI: 0.38-0.96). After adjusting for prognostic factors (sex, age. single versus doublet chemotherapy), ZCt patients still maintained a trend to better OS (p = 0.06) HR 0.63 (95%CI: 0.39-1.02) 34 versus 21 weeks.

Conclusions

The percentage of patients with MBD treated with ZA at first chemotherapy (37.7%) is low. The addition of ZA increased OS in NSCLC patients with MBD in this audit. More formal policies and dedicated trials on the treatment of MBD in NSCLC patients need to be put in place.     

Prognostic value of xanthine oxidoreductase expression in patients with non-small cell lung cancer

Background

Xanthine oxidoreductase (XOR) is a rate-limiting enzyme in the purine metabolism pathway. Lack of XOR expression is associated with unfavorable clinical outcomes. The objective of this study was to correlate XOR expression with prognosis in surgically resected non-small cell lung cancer (NSCLC).

Methods

Immunohistochemical staining was performed on deparaffinized specimens from 82 patients with stage I-IV NSCLC using a polyclonal anti-XOR rabbit antibody. Cytoplasmic XOR staining was scored on frequency and intensity scales from 0 to 4 with low expression defined as 0-1 and high expression defined as ≥2-4. XOR immunostaining was correlated with clinical characteristics and outcomes and analyzed using Kaplan-Meier and Cox proportional hazard methods.

Results

Positive XOR expression was observed in 53/82 cases (65%). Patients with high XOR frequency had a longer median survival of 3053 days (95% CI: 2190-3916) vs. 592 days (95% CI: 492-692 days) for patients with low XOR frequency, p = 0.0089, HR 0.47. Neither XOR intensity nor the overall score of XOR frequency multiplied by XOR intensity demonstrated any significant association with survival. Surgical resection was performed on 61 patients of which 34 (56%) received adjuvant chemotherapy. Patients who received adjuvant chemotherapy with low XOR expression, 15/34 (44%) had a shortened median survival compared with patients who received adjuvant chemotherapy with high XOR expression (543 days vs. 2023 days, respectively, p = 0.007 and HR = 0.33).

Conclusion

Low XOR expression was associated with shortened survival and also conferred a worse prognosis for patients with NSCLC who received adjuvant chemotherapy. Further studies of the XOR pathway are warranted to validate and mechanistically explain these outcomes.     

Prognostic importance of Mandard tumour regression grade following pre-operative chemo/radiotherapy for locally advanced rectal cancer

Purpose

To assess the prognostic value of the Mandard tumour regression score (TRG) following pre-operative chemo/radiotherapy in patients with locally advanced rectal cancer.

Methods and materials

The study involved 158 patients with locally advanced rectal cancer treated with pre-operative long course chemo/radiotherapy at Nottingham University Hospital between April 2001 and December 2008. Patients were treated with radiotherapy to a dose of 50 Gy in 25 fractions over 5 weeks with or without concurrent capecitabine chemotherapy at a dose of 1650 mg/m²/day. Surgery was normally performed after an interval of 6-10 weeks. The response to pre-operative treatment was carefully graded by a single pathologist using the five point Mandard score. The median follow-up was 40 months (range 3-90 months).

Results

Of the 158 patients 14% were TRG1, 41% were TRG2, 31% were TRG3, 13% were TRG4 and 1% were TRG5. The groups were combined into TRG1, TRG2 and TRG3-5 to simplify further analysis. The Mandard score was clearly related to both disease-free (p < 0.001) and overall survival (p = 0.012). On multivariate analysis perineural invasion, nodal status, TRG and circumferential resection margin status were the most powerful predictors of disease-free survival.

Conclusions

The Mandard tumour regression score is an independent prognostic factor and predicts for long-term outcome following pre-operative chemo/radiotherapy in rectal cancer.     

Cancer of unknown primary patients with midline nodal distribution: Midway between poor and favourable prognosis?

Background

Midline nodal cancer of unknown primary (CUP) has varying definitions and an unclear natural history compared to that of extragonadal germ cell cancer (EGCC) and neuroendocrine tumors.

Methods

We systematically reviewed all published series of patients with midline nodal CUP using three distinct definitions and presented our own retrospective cohort.

Results

Sixty four fit patients (median age 64) with poorly differentiated carcinoma or adenocarcinoma in midline nodal areas were treated from 1998 to 2008 at our center. Only two patients had elevated serum germ cell markers. Forty-eight percentage of patients responded to platinum-based chemotherapy (CR 11%). The median survival was 12 months (2-year survival 18%). Good PS (Hazard Ratio HR 0.287, p = 0.058) and administration of platinum (HR 0.340, p = 0.08) predicted for more favourable outcome. A subgroup of 15 male patients selected with stricter criteria had a CR rate of 33% and median survival of 18 months (2-year survival 24%). We identified 10 series of midline nodal CUP patients defined with discordant criteria. Despite high response rates (35-65%) to platinum chemotherapy, the median survival clustered around 12 months. Predictive factors for superior survival were low tumor bulk, patient fitness, female gender, carcinomatous histology, and absence of visceral metastases. There were differences between midline nodal CUP patients and EGCC as well as neuroendocrine tumors (age, tumor markers, response to therapy, long-term survival).

Conclusions

Midline nodal CUP patients are poorly defined, fare less well than EGCC or neuroendocrine cancer and probably constitute a heterogeneous entity with a minority harbouring atypical germ cell cancer.     

Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: A randomised phase III trial

Purpose

This multicentre, prospective, randomised-controlled trial compared efficacy and toxicity of differing radiotherapy doses in non-Hodgkin lymphoma (NHL).

Patients and methods

Patients with any histological subtype of NHL, requiring radiotherapy for local disease control, whether radical, consolidative or palliative, were included. Three hundred and sixty one sites of indolent NHL (predominantly follicular NHL and marginal zone lymphoma) were randomised to receive 40-45 Gy in 20-23 fractions or 24 Gy in 12 fractions. Six hundred and forty sites of aggressive NHL (predominantly diffuse large B cell lymphoma as part of combined-modality therapy) were randomised to receive 40-45 Gy in 20-23 fractions or 30 Gy in 15 fractions. Patients with all stages of disease, having first-line and subsequent therapies were included; first presentations of early-stage disease predominated.

Results

There was no difference in overall response rate (ORR) between standard and lower-dose arms. In the indolent group, ORR was 93% and 92%, respectively, (p = 0.72); in the aggressive group, ORR was 91% in both arms (p = 0.87). With a median follow-up of 5.6 years, there was no significant difference detected in the rate of within-radiation field progression (HR = 1.09, 95%CI = 0.76-1.56, p = 0.64 in the indolent group; HR = 0.98, 95%CI = 0.68-1.4, p = 0.89 in the aggressive group). There was also no significant difference detected in the progression free or overall survival. There was a trend for reduced toxicities in the low-dose arms; only the reduction in reported erythema reached significance.

Conclusion

In a large, randomised trial, there was no loss of efficacy associated with radiotherapy doses of 24 Gy in indolent NHL and 30 Gy in aggressive NHL, compared with previous standard doses of 40-45 Gy.