Re-irradiation combined with capecitabine in locally recurrent squamous cell carcinoma of the head and neck

Background

We performed a prospective phase II trial to investigate the safety and efficacy of radiotherapy combined with capecitabine in patients suffering from a recurrence of a squamous cell carcinoma of the head and neck (SCCHN) within a previously irradiated field.

Patients and methods

A total of 31 evaluable patients with recurrent SCCHN received re-irradiation with a total dose of 50?Gy (25 fractions over 5?weeks) up to a maximum of 60?Gy combined with 900?mg/m²/day capecitabine given on the days of radiotherapy.

Results

The median time to relapse after the first course of radiotherapy was 15?months. The overall response rate in our study was 68% including 6?patients with a complete response. The median overall survival was 8.4?months. Grade 3 or 4 mucositis occurred in 4?patients and 1?patient, respectively. No grade 4 hematological toxicities were observed; 1?patient had grade 3 anemia. The cumulative median lifetime dose was 116?Gy.

Conclusion

Capecitabine combined with re-irradiation is a well-tolerated treatment in patients with recurrent SCCHN. In light of its good tolerability, it appears to be a potential option for patients with a reduced performance status and may also serve as a basis for novel treatment concepts, such as in combination with targeted therapies.     

Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases

Purpose

The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases >?3?cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases.

Materials and methods

In two consecutive periods, 41?patients with 46?brain metastases received SRT with 1 fraction of 15?Gy, while 51?patients with 65?brain metastases received FSRT with 3?fractions of 8?Gy. We included patients with brain metastases with a planning target volume of >?13?cm³ or metastases in the brainstem.

Results

The minimum follow-up of patients still alive was 22?months. Comparing 1?fraction of 15?Gy ?with 3?fractions of 8?Gy, the 1-year rates of freedom from any local progression (54% and 61%, p?=?0.93) and pseudo progression (85% and 75%, p?=?0.25) were not significantly different. Overall survival rates were also not different.

Conclusion

The 1-year local progression and pseudo progression rates after 1 fraction of 15?Gy or 3?fractions of 8?Gy for large brain metastases and metastases in the brainstem are similar. For better local control rates, FSRT schemes with a higher biological equivalent dose may be necessary.     

Prolonged survival when temozolomide is added to accelerated radiotherapy for glioblastoma multiforme

Background

The goal of this study was to evaluate accelerated radiotherapy with and without temozolomide (TMZ) for glioblastoma multiforme (GBM).

Methods

This retrospective analysis evaluated 86 patients with histologically proven GBM who were treated with accelerated radiotherapy of 1.8 Gy twice daily to a total dose of 54 Gy within 3 weeks. Median age was 62 years and median Karnofsky index was 90. A total of 41 patients received radiotherapy only from 2002?C2005 and 45 patients were treated with TMZ concomitantly and after radiotherapy from 2005?C2007.

Results

Median overall survival (OS) was 12.5 months and 2-year OS was 15.4%. Patient characteristics were well balanced between the two groups except for better performance status (p = 0.05) and higher frequency of retreatment for the first recurrence (p = 0.02) in the TMZ group. Age at diagnosis (HR 2.83) and treatment with TMZ (HR 0.60) were correlated with OS in the multivariate analysis: treatment with and without TMZ resulted in median OS of 16 months and 11.3 months, respectively. Hematological toxicity grade > II was observed in 2/45 patients and 5/37 patients during simultaneous radiochemotherapy and adjuvant TMZ.

Conclusion

TMZ added to accelerated radiotherapy for GBM resulted in prolonged overall survival with low rates of severe hematological toxicity.     

Patterns of relapse and late toxicity after resection and whole-brain radiotherapy for solitary brain metastases

Background

This retrospective analysis was performed in order to evaluate the pattern of relapse and the risk of late toxicity for solitary brain metastases treated with surgery and whole-brain radiotherapy and to correlate the results with those from radiosurgical trials.

Patients and Methods

From a total of 66 patients, 52 received 10×3 Gy and 10 were treated with 20×2 Gy whole-brain radiotherapy after resection of their brain metastases.

Results

The actuarial probability of relapse was 27% and 55% after 1 and 2 year(s), respectively. The local relapse rate (at the original site of resected brain metastases) was rather high for melanoma, non-breast adenocarcinoma, and squamous-cell carcinoma. No local relapse occurred in breast cancer and small-cell carcinoma. Failure elsewhere in the brain seemed to be influenced by extracranial disease activity. Size of brain metastases and total dose showed no correlation with relapse rate. Occurrence of brain relapse was not associated with a reduced survival time, because 10/15 patients who developed a relapse received salvage therapy. Of the patients, 11 had symptoms of late radiation toxicity (the actuarial probability was 42% after 2 years).

Conclusions

Most results of surgical and radiosurgical studies are comparable to ours. Several randomized trials investigate surgical resection versus radiosurgery, as well as the effects of additional whole-brain radiotherapy in order to define the treatment of choice. Some data support the adjuvant application of 10×3 Gy over 2 weeks as a reasonable compromise when local control, toxicity, and treatment time have to be considered.     

Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer

Background and purpose

To evaluate the treatment outcomes of radiotherapy and prognostic factors for recurrent pancreatic cancer.

Patients and methods

The study comprised 30 patients who developed a locoregional recurrence of primarily resected pancreatic cancer and received radiotherapy between 2000 and 2013 with a median dose of 54 Gy (range, 39–60 Gy). Concurrent chemotherapy included gemcitabine for 18 patients and S-1 for seven patients. The treatment outcomes and prognostic factors were retrospectively analyzed.

Results

The median follow-up after radiotherapy was 14.6 months. The 1-year overall survival, local control, and progression-free survival rates were 69?%, 67?%, and 32?%, respectively. The median overall survival and progression-free survival rates were 15.9 and 6.9 months, respectively. Tumor marker reduction and ≥?50?% reduction were observed in 18 and two patients, respectively. Of the seven patients who exhibited pain symptoms, four and two patients were partly and completely relieved, respectively. Late grade 3 ileus and gastroduodenal bleeding were observed in one patient each. Among the clinicopathological factors evaluated, only a disease-free interval of greater than?18.9 months exhibited a significant association with improved overall survival (p?=?0.017).

Conclusions

Radiotherapy for isolated locally recurrent pancreatic cancer resulted in encouraging local control, overall survival, and palliative effects with mild toxicity, particularly in patients with a prolonged disease-free interval. This treatment strategy should be prospectively evaluated.     

Intensity modulated radiotherapy as neoadjuvant chemoradiation for the treatment of patients with locally advanced pancreatic cancer

Background

To evaluate outcome after intensity modulated radiotherapy (IMRT) compared to 3D conformal radiotherapy (3D-RT) as neoadjuvant treatment in patients with locally advanced pancreatic cancer (LAPC).

Materials and methods

In total, 57 patients with LAPC were treated with IMRT and chemotherapy. A median total dose of 45 Gy to the PTV__baseplan and 54 Gy to the PTV__boost in single doses of 1.8 Gy for the PTV__baseplan and median single doses of 2.2 Gy in the PTV__boost were applied. Outcomes were evaluated and compared to a large cohort of patients treated with 3D-RT.

Results

Overall treatment was well tolerated in all patients and IMRT could be completed without interruptions. Median overall survival was 11 months (range 5–37.5 months). Actuarial overall survival at 12 and 24 months was 36?% and 8?%, respectively. A significant impact on overall survival could only be observed for a decrease in CA 19-9 during treatment, patients with less pre-treatment CA 19-9 than the median, as well as weight loss during treatment. Local progression-free survival was 79?% after 6 months, 39?% after 12 months, and 13?% after 24 months. No factors significantly influencing local progression-free survival could be identified. There was no difference in overall and progression-free survival between 3D-RT and IMRT. Secondary resectability was similar in both groups (26?% vs. 28?%). Toxicity was comparable and consisted mainly of hematological toxicity due to chemotherapy.

Conclusion

IMRT leads to a comparable outcome compared to 3D-RT in patients with LAPC. In the future, the improved dose distribution, as well as advances in image-guided radiotherapy (IGRT) techniques, may improve the use of IMRT in local dose escalation strategies to potentially improve outcome.     

Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation?

Background

After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation.

Materials and methods

In all, 12 consecutive stage I–IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a “selective” PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an “elective” PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a “selective” pleural irradiation plan (SPI plan) and an “elective” pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]).

Results

In the SPI plans, the average median dose to the S?PTV was 53.6?Gy (range 41–63.6?Gy). In 4 of 12 patients, it was possible to escalate the dose to the S?PTV to >58?Gy. In the EPI plans, the average median doses to the E?PTV and to the S?PTV were 48.6?Gy (range 38.5–58.7) and 49?Gy (range 38.6–59.5?Gy), respectively. No significant dose escalation was achievable.

Conclusion

The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49?Gy to more than 58?Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM.

     

Protocol-based image-guided salvage brachytherapy

Purpose

To assess the overall clinical outcome of protocol-based image-guided salvage pulsed-dose-rate brachytherapy for locally recurrent prostate cancer after radiotherapy failure particularly regarding feasibility and side effects.

Patients and methods

Eighteen consecutive patients with locally recurrent prostate cancer (median age, 69 years) were treated during 2005–2011 with interstitial PDR brachytherapy (PDR-BT) as salvage brachytherapy after radiotherapy failure. The treatment schedule was PDR-BT two times with 30 Gy (pulse dose 0.6 Gy/h, 24 h per day) corresponding to a total dose of 60 Gy. Dose volume adaptation was performed with the aim of optimal coverage of the whole prostate (V₁₀₀ >?95?%) simultaneously respecting the protocol-based dose volume constraints for the urethra (D_0.1 cc <?130?%) and the rectum (D_2 cc <?50–60?%) taking into account the previous radiation therapy. Local relapse after radiotherapy (external beam irradiation, brachytherapy with J-125 seeds or combination) was confirmed mostly via choline-PET and increased PSA levels. The primary endpoint was treatment-related late toxicities—particularly proctitis, anal incontinence, cystitis, urinary incontinence, urinary frequency/urgency, and urinary retention according to the Common Toxicity Criteria. The secondary endpoint was PSA-recurrence-free survival.

Results

We registered urinary toxicities only. Grade 2 and grade 3 toxicities were observed in up to 11.1?% (2/18) and 16.7?% (3/18) of patients, respectively. The most frequent late-event grade 3 toxicity was urinary retention in 17?% (3/18) of patients. No late gastrointestinal side effects occurred. The biochemical PSA-recurrence-free survival probability at 3 years was 57.1?%. The overall survival at 3 years was 88.9?%; 22?% (4/18) of patients developed metastases. The median follow-up time for all patients after salvage BT was 21 months (range, 8–77 months).

Conclusion

Salvage PDR-brachytherapy of the prostate following local failure after radiation therapy is a treatment option with a low rate of genitourinary side effects and no late gastrointestinal side effects. The treatment efficacy in the first 3 years is promising.     

Survival and prognostic factors after moderately hypofractionated palliative thoracic radiotherapy for non-small cell lung cancer

Background

Survival and prognostic variables in patients with advanced or metastatic non-small cell lung cancer (NSCLC) requiring thoracic palliative radiotherapy using a moderately hypofractionated regime (13–15?×?3 Gy) were evaluated.

Methods

From March 2006 to April 2012, 120 patients with a physician estimated prognosis of 6–12 months were treated with this regime using CT-based 3D conformal radiotherapy. We collected data on patient characteristics, comorbidities, toxicity, and treatment parameters.

Results

Radiotherapy was completed as prescribed in 114 patients (95.0?%, premature termination 5.0?%). Acute grade 3 toxicity was seen in 6.4?% of patients. The median survival of all patients was 5.8 months. Nonmetastatic patients survived significantly longer than patients with metastatic disease (median 11.7 months vs 4.7 months, p?=?0.0001) and 18.6?% of nonmetastatic patients survived longer than 2 years. In 12.7?% radiotherapy started less than 30 days before death and 14.2?% of patients received radiotherapy within 14 days before death. In the multivariate analysis, good general condition, nonmetastatic disease, and a stable or improved general condition at the end of radiotherapy were significant. The treatment parameters, age, and comorbidities were not statistically significant.

Conclusion

Our data confirm considerable effectiveness of 13?×?3 Gy with conformal radiotherapy for patients with locally confined NSCLC not fit for radical treatment and raise doubt for this regimen in metastatic patients and ECOG ≥?2 when burden, acute toxicity, and resources are considered.     

Intraoperative Radiotherapie (IORT) lokal ausgedehnter und rezidivierter Nierenzellkarzinome

Purpose

Renal cell carcinomas are relatively radioresistant. After macroscopically incomplete tumor resection conventional external beam radiotherapy is dose-limited and additional systemic treatment with chemotherapy ineffective to achieve local control. In a pilot study the role of intraoperative radiotherapy in the treatment of locally advanced or recurrent renal cell carcinomas was analysed.

Patients and Method s

From January 1992 to July 1994 11 patients with a primary (n=3) or recurrent renal cell carcinoma had IORT. One patient had complete resection and in 3 respectively 7 patients microscopically or macroscopically residual disease was left. Using 6 to 10 MeV, a single dose of 15 to 20 Gy was delivered to the fossa renalis and the corresponding paraaortic area. Based on three-dimensional treatment planning, additional external beam radiotherapy was given 3 to 4 weeks later (40) Gy, 2 Gy SD, 23 MV).

Results

After a mean follow-up of 24.3 months 5 patients had died of distant metastases (lung, liver, bone, mediastinum) with a mean survival time of 11.5 months. Mean disease-free interval was 6.4 months. One patient suffered from a second malignancy. Two patients are alive with distant metastases. Local tumor control in the entire group was 100%. The calculated 4-year overall and disease-free survival was 47% and 34%. The postoperative course was affected in 3 patients (abscess n=1, short dehiscence of the abdominal wound n=2). The gastrointestinal toxicity during external beam radiotherapy was low. No IORT-specific late adverse effects were observed.

Conclusion

After incomplete tumor resection local tumor control with minimal therapy related side effects could be achieved using intraoperative radiotherapy. With IORT the dose limitation in the radiotherapy of renal cell carcinoma could be overcome. The high distant metastases rate relativized overall prognosis. The low morbidity rate justifies further evaluation of this technique.     

Präoperative Bestrahlung mit interstitiellem Radiohyperthermie-Boost bei Mammatumoren ≥3 cm

Aim

The aim of this protocol was to investigate breast conservation rates with and without flap-supported surgery after preoperative chemotherapy, radiotherapy and hyperthermia.

Patients and Methods

One hundred and fifty-eight patients with stage IIA-IV breast cancers were initially treated with chemotherapy, radiotherapy and hyperthermia. Radiation treatment consisted of an interstitial boost of 10 Gy¹⁹²Ir-afterloading therapy and a course of external beam radiotherapy of 50 Gy, using 5 × 2 Gy/week. Local hyperthermia with 43.5–44.5°C over 60 minutes was delivered immediately before interstitial radiotherapy.

Results

One hundred and forty-two patients underwent salvage surgery. A breast-conserving approach was possible in 74 patients (52%). Fifty-three patients (37%) underwent flap-supported surgery. After a median follow-up of 20 months, one patient developed isolated local recurrence. In 14 cases, locoregional recurrences occurred in combination with distant metastases.

Conclusion

In about 50%, breast conservation was achieved by chemotherapy, radiotherapy and hyperthermia. The low isolated local recurrence rate of 0.6% (1/158) has to be substantiated by further follow-up.     

Biologically effective dose and definitive radiation treatment for localized prostate cancer

Background and purpose

It is not clear if prolongation of definitive external radiation therapy for prostate cancer has an effect on biochemical failure. The aim of this work was to evaluate whether the biologically effective dose (BED), and in particular the duration of radiotherapy, intended as overall treatment time, has an effect on biochemical failure rates and to develop a nomogram useful to predict the 6-year probability of biochemical failure.

Patients and methods

A total of 670 patients with T1–3 N0 prostate cancer were treated with external beam definitive radiotherapy, to a total dose of 72–79.2 Gy in 40–44 fractions. The computed BED values were treated with restricted cubic splines. Variables were checked for colinearity using Spearman’s test. The Kaplan–Meier method was used to calculate freedom from biochemical relapse (FFBR) rates. The Cox regression analysis was used to identify prognostic factors of biochemical relapse in the final most performing model and to create a nomogram. Concordance probability estimate and calibration methods were used to validate the nomogram.

Results

Neoadjuvant and concomitant androgen deprivation was administered to 475 patients (70?%). The median follow-up was 80 months (range 20–129 months). Overall, the 6-year FFBR rate was 88.3?%. BED values were associated with higher biochemical failure risk. Age, iPSA, risk category, and days of radiotherapy treatment were independent variables of biochemical failure.

Conclusion

A prolongation of RT (lower BED values) is associated with an increased risk of biochemical failure. The nomogram may be helpful in decision making for the individual patient.     

Fractionated stereotactic radiotherapy in the treatment of pituitary adenomas

Purpose

The purpose of this work was to evaluate tumor control and side effects associated with fractionated stereotactic radiotherapy (FSRT) in the management of residual or recurrent pituitary adenomas.

Patients and methods

We report on 37 consecutive patients with pituitary adenomas treated with FSRT at our department. All patients had previously undergone surgery. Twenty-nine patients had nonfunctioning, 8 had hormone-producing adenoma. The mean total dose delivered by a linear accelerator was 49.4 Gy (range 45–52.2 Gy), 5?×?1.8 Gy weekly. The mean PTV was 22.8 ccm (range 2.0–78.3 ccm). Evaluation included serial imaging tests, endocrinologic and ophthalmologic examination.

Results

Tumor control was 91.9?% for a median follow-up time of 57 months (range 2–111 months). Before FSRT partial hypopituitarism was present in 41?% of patients, while 35?% had anterior panhypopituitarism. After FSRT pituitary function remained normal in 22?%, 43?% had partial pituitary dysfunction, and 35?% had anterior panhypopituitarism. Visual acuity was stable in 76?% of patients, improved in 19?%, and deteriorated in 5?%. Visual fields remained stable in 35 patients (95?%), improved in one and worsened in 1 patient (2.7?%).

Conclusion

FSRT is an effective and safe treatment for recurrent or residual pituitary adenoma. Good local tumor control and preservation of adjacent structures can be reached, even for large tumors.     

Radiotherapy with and without temozolomide in elderly patients with glioblastoma

Background and purpose

The optimal treatment for elderly patients (age ???70?years) with glioblastoma (GBM) remains controversial. We conducted a retrospective analysis in 43 consecutive elderly patients with glioblastoma who either underwent radiotherapy (RT) or radiotherapy plus concomitant temozolomide (TMZ).

Patients and methods

A total of 43?patients (???70?years of age, median age 75.8?years) with newly diagnosed glioblastoma and a Karnofsky performance status (KPS) ???70 were treated with RT alone (median 60?Gy in 2?Gy single fractions) or RT plus TMZ at a dose of 75?mg/m² per day. The two groups were well-balanced; univariate (log-rank test) and multivariate Cox proportional hazards analysis were used to identify relevant prognostic factors.

Results

The median overall survival (mOS) of the entire patient cohort was 264?days (8.8?months) and the median progression-free survival (PFS) was 192?days (6.4?months). The factors age, sex, previous surgery, KPS, and concomitant use of TMZ had no significant influence on OS/PFS; multivariate analysis was performed to obtain adjusted hazard ratios. TMZ use resulted in a trend toward poorer overall survival when applied concomitantly (314?days compared to 192?days within the TMZ group, p?=?0.106). The subgroup analysis revealed that TMZ use resulted in significantly worse survival rates in patients with KPS70 (p?=?0.027), but for patients with KPS80 this difference was not detectable.

Conclusion

TMZ should only be used carefully in elderly patients with unfavorable KPS. In this patient cohort, radiotherapy alone is a reasonable option. Standard RT plus concomitant TMZ may be an advantageous treatment option for elderly patients with newly diagnosed glioblastoma who present with good prognostic factors.     

Factors affecting the local control of stereotactic body radiotherapy for lung tumors including primary lung cancer and metastatic lung tumors

Purpose

To identify factors affecting local control of stereotactic body radiotherapy (SBRT) for lung tumors including primary lung cancer and metastatic lung tumors.

Materials and methods

Between June 2006 and June 2009, 159 lung tumors in 144 patients (primary lung cancer, 128; metastatic lung tumor, 31) were treated with SBRT with 48?C60?Gy (mean 50.1?Gy) in 4?C5 fractions. Higher doses were given to larger tumors and metastatic tumors in principle. Assessed factors were age, gender, tumor origin (primary vs. metastatic), histological subtype, tumor size, tumor appearance (solid vs. ground glass opacity), maximum standardized uptake value of positron emission tomography using ¹⁸F-fluoro-2-deoxy-d-glucose, and SBRT doses.

Results

Follow-up time was 1?C60?months (median 18?months). The 1-, 2-, and 3-year local failure-free rates of all lesions were 90, 80, and 77?%, respectively. On univariate analysis, metastatic tumors (p?p?=?0.0246), and higher SBRT doses (p?=?0.0334) were the statistically significant unfavorable factors for local control. On multivariate analysis, only tumor origin was statistically significant (p?=?0.0027). The 2-year local failure-free rates of primary lung cancer and metastatic lung tumors were 87 and 50?%, respectively.

Conclusions

A metastatic tumor was the only independently significant unfavorable factor for local control after SBRT.     

External-beam radiation therapy after surgical resection and intraoperative electron-beam radiation therapy for oligorecurrent gynecological cancer

Purpose

The goal of the present study was to analyze prognostic factors in patients treated with external-beam radiation therapy (EBRT), surgical resection and intraoperative electron-beam radiotherapy (IOERT) for oligorecurrent gynecological cancer (ORGC).

Patients and methods

From January 1995 to December 2012, 61 patients with ORGC [uterine cervix (52?%), endometrial (30?%), ovarian (15?%), vagina (3?%)] underwent IOERT (12.5 Gy, range 10–15 Gy), and surgical resection to the pelvic (57?%) and paraaortic (43?%) recurrence tumor bed. In addition, 29 patients (48?%) also received EBRT (range 30.6–50.4 Gy). Survival outcomes were estimated using the Kaplan–Meier method, and risk factors were identified by univariate and multivariate analyses.

Results

Median follow-up time for the entire cohort of patients was 42 months (range 2–169 months). The 10-year rates for overall survival (OS) and locoregional control (LRC) were 17 and 65?%, respectively. On multivariate analysis, no tumor fragmentation (HR 0.22; p?=?0.03), time interval from primary tumor diagnosis to locoregional recurrence (LRR) <?24 months (HR 4.02; p?=?0.02) and no EBRT at the time of pelvic recurrence (HR 3.95; p?=?0.02) retained significance with regard to LRR. Time interval from primary tumor to LRR <?24 months (HR 2.32; p?=?0.02) and no EBRT at the time of pelvic recurrence (HR 3.77; p?=?0.04) showed a significant association with OS after adjustment for other covariates.

Conclusion

External-beam radiation therapy at the time of pelvic recurrence, time interval for relapse ≥?24 months and not multi-involved fragmented resection specimens are associated with improved LRC in patients with ORGC. As suggested from the present analysis a significant group of ORGC patients could potentially benefit from multimodality rescue treatment.     

An individualized radiation dose escalation trial in non-small cell lung cancer based on FDG-PET imaging

Aim

The aim of the study was to assess the feasibility of an individualized 18F fluorodeoxyglucose positron emission tomography (FDG-PET)-guided dose escalation boost in non-small cell lung cancer (NSCLC) patients and to assess its impact on local tumor control and toxicity.

Patients and methods

A total of 13 patients with stage II–III NSCLC were enrolled to receive a dose of 62.5?Gy in 25 fractions to the CT-based planning target volume (PTV; primary turmor and affected lymph nodes). The fraction dose was increased within the individual PET-based PTV (PTV_PET) using intensity modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) until the predefined organ-at-risk (OAR) threshold was reached. Tumor response was assessed during follow-up by means of repeat FDG-PET/computed tomography. Acute and late toxicity were recorded and classified according to the CTCAE criteria (Version 4.0). Local progression-free survival was determined using the Kaplan-Meier method.

Results

The average dose to PTV_PET reached 89.17?Gy for peripheral and 75?Gy for central tumors. After a median follow-up period of 29 months, seven patients were still alive, while six had died (four due to distant progression, two due to grade 5 toxicity). Local progression was seen in two patients in association with further recurrences. One and 2-year local progression free survival rates were 76.9% and 52.8%, respectively. Three cases of acute grade 3 esophagitis were seen. Two patients with central tumors developed late toxicity and died due to severe hemoptysis.

Conclusion

These results suggest that a non-uniform and individualized dose escalation based on FDG-PET in IMRT delivery is feasible. The doses reached were higher in patients with peripheral compared to central tumors. This strategy enables good local control to be achieved at acceptable toxicity rates. However, dose escalation in centrally located tumors with direct invasion of mediastinal organs must be performed with great caution in order to avoid severe late toxicity.

     

Primäre Strahlentherapie eines rezidivierenden Merkel-Zell-Karzinoms des Lides

Background

Despite an increasing number of reports Merkel-cell-carcinoma still is a rare neoplasm. Reports on radical radiotherapy are sparse.

Patient and Method

We report on a successful radical radiotherapy of a recurrent Merkel-cell-carcinoma of the eyelid in an 84-year old woman, using a hypofractionated treatment of 50 Gy with 70 kV-X-rays, 10 fractions of 5 Gy within 5 weeks.

Result

Rapid and complete remission was achieved, with no signs of local or distant failure 24 months after the end of therapy.

Conclusion

The case reported on highlights the radiosensitivity of this tumor and the role of radiotherapy not merely as salvage procedure.     

Moderately hypofractionated radiotherapy for localized prostate cancer

Purpose

To evaluate long-term outcome after dose-escalated, moderately hypofractionated radiotherapy for prostate cancer.

Methods

Since 2005, 150 consecutive patients were treated with primary radiotherapy for localized prostate cancer. Intensity modulated radiotherapy (IMRT) using the simultaneous integrated boost (SIB) technique was practiced in all patients and doses of 73.9 Gy (n?=?41) and 76.2 Gy (n?=?109) were delivered in 32 and 33 fractions, respectively. The pelvic lymph nodes were treated in 41 high-risk patients. Treatment was delivered using cone-beam CT based image-guided radiotherapy (IGRT). Toxicity was assessed prospectively using CTCAE 3.0; biochemical failure was defined according to the Phoenix definition of nadir +?2 ng/ml.

Results

Median follow-up of living patients was 50 months. Gastrointestinal (GI) toxicity was mild with >?80?% of the patients free from any GI toxicity during follow-up and no time trend to increased rates or to higher grade of GI toxicity. Two patients suffered from late grade 3 GI toxicity. Acute genitourinary (GU) toxicity grade 1–2 was observed in 85?% of the patients; most patients recovered quickly within 6 weeks after treatment. The rate of GU toxicity grade ≥?2 was <?10?% at 6–12 month but increased continuously to 22.4?% at 60 months; grade 3 GU toxicity remained below 5?% during follow-up. The 5-year freedom from biochemical failure (FFBF) was 82?% for all patients and 88, 80, and 78?% for low-, intermediate-, and high-risk disease.

Conclusion

Favorable FFBF with simultaneously low rates of toxicity was observed after moderately hypofractionated radiotherapy with 2 Gy-equivalent doses ≥?80 Gy. Conformal IMRT planning and accurate IGRT treatment delivery may have contributed to these results.     

Salvage radiotherapy in patients with recurrent esophageal carcinoma

Purpose

The feasibility and effectiveness of radiotherapy in the management of recurrent esophageal carcinoma (REC) is reported.

Patients and methods

A consecutive cohort of 54?patients with rcT1-4, rcN0-1, or cM0 recurrent esophageal carcinoma (69% squamous cell carcinoma, 31% adenocarcinoma) was treated between 1988 and 2010. The initial treatment for these patients was definitive radiochemotherapy, surgery alone, or neoadjuvant radiochemotherapy?+?surgical resection in 8 (15%), 33 (61%), and 13 (24%) patients, respectively. The median time to recurrence from initial treatment was 19?months (range 4?C79?months). The site of the recurrence was anastomotic or local, nodal, or both in 63%, 30%, and 7% of patients, respectively. Salvage radio(chemo)therapy was carried out with a median dose of 45?Gy (range 30?C68?Gy).

Results

Median follow-up time for surviving patients from the start of R(C)T was 38?months (range 10?C105?months). Relief of symptoms was achieved in 19 of 28 symptomatic patients (68%). The median survival time was 12?months (95%?confidence interval (CI) 7?C17?months) and the median recurrence-free interval was 8?months (95%?CI 4?C12?months). The survival rates at 1, 2, and 3?years were 55?±?7%, 29?±?6%, and 19?±?5%, respectively. The recurrence-free survival rates at 1, 2, and 3?years were 44?±?7%, 22?±?6%, and 15?±?5%, respectively. A radiation dose ???45?Gy and conformal RT were associated with a better prognosis.

Conclusion

RT is feasible and effective in the management of recurrent esophageal carcinoma, especially for relief of symptoms. Toxicity is in an acceptable range. The outcome of REC is poor; however, long-term survival of patients with recurrent esophageal carcinoma after radiochemotherpy might be possible, even with a previous history of radiotherapy in the initial treatment. If re-irradiation of esophageal carcinoma is contemplated, three-dimensional conformal techniques and a minimum total dose of 45?Gy are recommended.