Executive summary of American Radium Society's appropriate use criteria for the postoperative management of lower grade gliomas.

Postoperative management of lower grade gliomas (grade 2 and 3) is heterogeneous. The American Radium Society's brain malignancies panel systematically reviewed and evaluated the literature to develop consensus guidelines addressing timing of postoperative therapy, monotherapy versus combined modality therapy, type of chemotherapy used with radiotherapy, and radiotherapy dose. Thirty-six studies were included. Using consensus methodology (modified Delphi), the panel voted upon representative case variants using a 9-point appropriateness scale to address key questions. Voting results were collated to develop summarized recommendations. Following gross-total surgical resection, close surveillance is appropriate for well-selected grade 2, IDH-mutant oligodendrogliomas or astrocytomas with low-risk features. For grade 2 gliomas with high-risk features or any grade 3 glioma, immediate adjuvant therapy is recommended. When postoperative therapy is administered, radiation and planned chemotherapy is strongly recommended over monotherapy. For grade 2 and 3 IDH-mutant oligodendrogliomas and astrocytomas, either adjunctive PCV (procarbazine, lomustine, vincristine) or temozolomide is appropriate. For grade 3 IDH-mutant astrocytomas, radiotherapy followed by temozolomide is strongly recommended. The recommended radiotherapy dose for grade 2 gliomas is 45-54 Gy/1.8-2.0 Gy, and for grade 3 gliomas is 59.4-60 Gy/1.8-2.0 Gy. While multiple appropriate treatment options exist, these consensus recommendations provide an evidence-based framework to approach postoperative management of lower grade gliomas.

Executive summary from American Radium Society's appropriate use criteria on neurocognition after stereotactic radiosurgery for multiple brain metastases.

BACKGROUND: The American Radium Society (ARS) Appropriate Use Criteria brain malignancies panel systematically reviewed (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) published literature on neurocognitive outcomes after stereotactic radiosurgery (SRS) for patients with multiple brain metastases (BM) to generate consensus guidelines. METHODS: The panel developed 4 key questions (KQs) to guide systematic review. From 11 614 original articles, 12 were selected. The panel developed model cases addressing KQs and potentially controversial scenarios not addressed in the systematic review (which might inform future ARS projects). Based upon quality of evidence, the panel confidentially voted on treatment options using a 9-point scale of appropriateness. RESULTS: The panel agreed that SRS alone is usually appropriate for those with good performance status and 2-10 asymptomatic BM, and usually not appropriate for >20 BM. For 11-15 and 16-20 BM there was (between 2 case variants) agreement that SRS alone may be appropriate or disagreement on the appropriateness of SRS alone. There was no scenario (among 6 case variants) in which conventional whole-brain radiotherapy (WBRT) was considered usually appropriate by most panelists. There were several areas of disagreement, including: hippocampal sparing WBRT for 2-4 asymptomatic BM; WBRT for resected BM amenable to SRS; fractionated versus single-fraction SRS for resected BM, larger targets, and/or brainstem metastases; optimal treatment (WBRT, hippocampal sparing WBRT, SRS alone to all or select lesions) for patients with progressive extracranial disease, poor performance status, and no systemic options. CONCLUSIONS: For patients with 2-10 BM, SRS alone is an appropriate treatment option for well-selected patients with good performance status. Future study is needed for those scenarios in which there was disagreement among panelists.

Stereotactic Body Radiotherapy for Spinal Metastases: Practice Guidelines, Outcomes, and Risks.

Spine metastases can be a debilitating and difficult therapeutic challenge for a significant number of cancer patients. Surgical management of spine metastases is often limited because of the complexity, risks, and recovery delays associated with open invasive surgical procedures. Conventional palliative external beam radiation therapy is the most common treatment modality. However, it is associated with limited palliative efficacy and local tumor control, including in the postoperative setting. In the era of improving systemic disease control, spine stereotactic body radiotherapy is fast emerging as the therapeutic modality of choice for selected de novo, postoperative, and salvage reirradiation spine metastases patients. Considerable expertise, multidisciplinary collaboration, and rigid adherence to quality metrics are required for the safe application of this highly conformal ablative therapy. This review highlights the current state of the evidence, understanding of the late effects, and technological requirements for spine stereotactic body radiotherapy specific to spinal metastases.

Stereotactic body radiotherapy as monotherapy or post-external beam radiotherapy boost for prostate cancer: technique, early toxicity, and PSA response.

PURPOSE: High dose rate (HDR) brachytherapy has been established as an excellent monotherapy or after external-beam radiotherapy (EBRT) boost treatment for prostate cancer (PCa). Recently, dosimetric studies have demonstrated the potential for achieving similar dosimetry with stereotactic body radiotherapy (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir, and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa using HDR brachytherapy fractionation. PATIENTS AND METHODS: To date, 38 patients have been treated with SBRT at the University of California-San Francisco with a minimum follow-up of 12 months. Twenty of 38 patients were treated with SBRT monotherapy (9.5 Gy × 4 fractions), and 18 were treated with SBRT boost (9.5 Gy × 2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44 HDR brachytherapy boost patients with disease characteristics similar to the SBRT boost cohort was also analyzed as a descriptive comparison. RESULTS: SBRT was well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42% and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two patients experienced late Grade 3 GU toxicity. All patients are without evidence of biochemical or clinical progression to date, and favorably low PSA nadirs have been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1) for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10 ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6 months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3). CONCLUSIONS: Early results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable PSA response and minimal toxicity. PSA nadir with SBRT boost appears comparable to those achieved with HDR brachytherapy boost.

Results of the 2005 to 2008 Association of Residents in Radiation Oncology surveys of chief residents in the United States: didactics and research experience.

OBJECTIVES: To analyze the didactics and research experience reported by chief residents during their residency training. METHODS: During the academic years 2005 to 2006, 2006 to 2007, and 2007 to 2008, the Association of Residents in Radiation Oncology (ARRO) conducted a nationwide survey of all radiation oncology chief residents in the United States. Chi-square statistic was used to assess for changes in didactics and research experience over time. RESULTS: During the years surveyed, an increasing percentage of programs offered curriculum-based didactics in clinical oncology (P=0.042), with a similar trend of borderline significance observed in biostatistics (P = 0.056). Each year, the majority of programs offered >40 hours of curriculum-based training in clinical oncology and physics, >20 hours in radiobiology, and 10 hours or fewer in biostatistics. 11% to 13% of residents reported having no full-time equivalent radiation biologists affiliated with their training program. Less than 64% of programs incorporated mock oral boards into their training. An increasing percentage of programs evaluated residents in a "360 degree" manner, with a trend to significance (P=0.073). Over 80% of programs required resident participation in research activities and allocated dedicated elective research time, typically 4 months or longer. Though the vast majority of programs make clinical research activities available to interested residents, borderline significance (P = 0.051) was observed for a decreasing percentage of such programs during the years analyzed. CONCLUSIONS: Trends in didactics and research experience over three years are documented to allow residents and program directors to assess their residency training.

Temporal compartmental dosing effects for robotic prostate stereotactic body radiotherapy.

The rate of dose accumulation within a given area of a target volume tends to vary significantly for non-isocentric delivery systems such as Cyberknife stereotactic body radiotherapy. In this study, we investigated whether intra-target temporal dose distributions produce significant variations in the biological equivalent dose. For the study, time courses of ten patients were reconstructed and calculation of a biologically equivalent uniform dose (EUD) was performed using a formula derived from the linear quadratic model (α/ß = 3 for prostate cancer cells). The calculated EUD values obtained for the actual patient treatments were then compared with theoretical EUD values for delivering the same physical dose distribution except that the whole target being irradiated continuously (e.g. large-field 'dose-bathing' type of delivery). For all the case, the EUDs for the actual treatment delivery were found to correlate strongly with the EUDs for the large-field delivery: a linear correlation coefficient of R² = 0.98 was obtained and the average EUD for the actual Cyberknife delivery was somewhat higher (5.0 ± 4.7%) than that for the large-field delivery. However, no statistical significance was detected between the two types of delivery (p = 0.21). We concluded that non-isocentric small-field Cyberknife delivery produced consistent biological dosing that tracked well with the constant-dose-rate, large-field-type delivery for prostate stereotactic body radiotherapy.

Results of the 2005-2008 Association of Residents in Radiation Oncology survey of chief residents in the United States: clinical training and resident working conditions.

PURPOSE: To document clinical training and resident working conditions reported by chief residents during their residency. METHODS AND MATERIALS: During the academic years 2005 to 2006, 2006 to 2007, and 2007 to 2008, the Association of Residents in Radiation Oncology conducted a nationwide survey of all radiation oncology chief residents in the United States. Chi-square statistics were used to assess changes in clinical training and resident working conditions over time. RESULTS: Surveys were completed by representatives from 55 programs (response rate, 71.4%) in 2005 to 2006, 60 programs (75.9%) in 2006 to 2007, and 74 programs (93.7%) in 2007 to 2008. Nearly all chief residents reported receiving adequate clinical experience in commonly treated disease sites, such as breast and genitourinary malignancies; and commonly performed procedures, such as three-dimensional conformal radiotherapy and intensity-modulated radiotherapy. Clinical experience in extracranial stereotactic radiotherapy increased over time (p < 0.001), whereas clinical experience in endovascular brachytherapy (p <0.001) decreased over time. The distribution of gynecologic and prostate brachytherapy cases remained stable, while clinical case load in breast brachytherapy increased (p = 0.006). A small but significant percentage of residents reported receiving inadequate clinical experience in pediatrics, seeing 10 or fewer pediatric cases during the course of residency. Procedures involving higher capital costs, such as particle beam therapy and intraoperative radiotherapy, and infrequent clinical use, such as head and neck brachytherapy, were limited to a minority of institutions. Most residency programs associated with at least one satellite facility have incorporated resident rotations into their clinical training, and the majority of residents at these programs find them valuable experiences. The majority of residents reported working 60 or fewer hours per week on required clinical duties. CONCLUSIONS: Trends in clinical training and resident working conditions over 3 years are documented to allow residents and program directors to assess their residency training.

Erlotinib eradicates brain metastases from epidermal growth factor receptor mutant non-small cell lung cancer.

Erlotinib is active in patients with lung cancer; especially those who demonstrate a mutation in exons 18-21 in the epidermal growth factor receptor (EGFR) gene. Patients with lung cancer and brain metastases have poor prognosis as systemic chemotherapy is ineffective in treating the central nervous system (CNS) metastases due to its inability to cross the blood brain barrier. Herein, we report a case of a 61 year old female who presented with stage IV adenocarcinoma of the lung with bilateral cerebral and cerebellar CNS involvement. The patient's tumor harbored a mutation in exon 19 in the EGFR gene. Treatment with erlotinib was started as soon as the molecular studies were available with remarkable and complete radiographic response in the CNS disease, and complete resolution of the previously detected metastases. The patient did not receive any other CNS intervention and radiation was not given due to the lack of CNS symptoms.

Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost.

PURPOSE: Permanent prostate implant brachytherapy (PPI), three-dimensional conformal radiotherapy (3D-CRT), and conformal proton beam radiotherapy (CPBRT) are used in the treatment of localized prostate cancer, although no head-to-head trials have compared these modalities. We studied the biochemical control (biochemical no evidence of disease [bNED]) and prostate-specific antigen (PSA) nadir achieved with contemporary PPI, and evaluated it against 3D-CRT and CPBRT. PATIENTS AND METHODS: A total of 249 patients were treated with PPI at the University of California, San Francisco, and the outcomes were compared with those from a 3D-CRT cohort and the published results of a high-dose CPBRT boost (CPBRTB) trial. For each comparison, subsets of the PPI cohort were selected with patient and disease criteria similar to those of the reference group. RESULTS: With a median follow-up of 5.3 years, the bNED rate at 5 and 7 years achieved with PPI was 92% and 86%, respectively, using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, and 93% using the PSA nadir plus 2 ng/mL definition. Using the ASTRO definition, a 5-year bNED rate of 78% was achieved for the 3D-CRT patients compared with 94% for a comparable PPI subset and 93% vs. 92%, respectively, using the PSA nadir plus 2 ng/mL definition. The median PSA nadir for patients treated with PPI and 3D-CRT was 0.10 and 0.40 ng/mL, respectively (p < .0001). For the CPBRT comparison, the 5-year bNED rate after a CPBRTB was 91% using the ASTRO definition vs. 93% for a similar group of PPI patients. A greater proportion of PPI patients achieved a lower PSA nadir compared with those achieved in the CPBRTB trial (PSA nadir < or =0.5 ng/mL, 91% vs. 59%, respectively). CONCLUSION: We have demonstrated excellent outcomes in low- to intermediate-risk patients treated with PPI, suggesting at least equivalent 5-year bNED rates and a greater proportion of men achieving lower PSA nadirs compared with 3D-CRT or CPBRTB.

High-dose-rate brachytherapy for localized prostate adenocarcinoma post abdominoperineal resection of the rectum and pelvic irradiation: Technique and experience.

PURPOSE: Treatment options are limited for patients with localized prostate cancer and a prior history of abdominoperineal resection (APR) and pelvic irradiation. We have previously reported on the successful utility of high-dose-rate (HDR) brachytherapy salvage for prostate cancer failing definitive external beam radiation therapy (EBRT). In this report, we describe our technique and early experience with definitive HDR brachytherapy in patients post APR and pelvic EBRT. PATIENTS AND METHODS: Six men with newly diagnosed localized prostate cancer had a prior history of APR and pelvic EBRT. Sixteen to 18 HDR catheters were placed transperineally under transperineal ultrasound-guidance. The critical first two catheters were placed freehand posterior to the inferior rami on both sides of the bulbar urethra under cystoscopic visualization. A template was used for subsequent catheter placement. Using CT-based planning, 5 men received 36Gy in six fractions as monotherapy. One patient initially treated with EBRT to 30Gy, received 24Gy in four fractions. RESULTS: Median age was 67.5 (56-74) years. At a median followup of 26 (14-60) months, all patients are alive and with no evidence of disease per the Phoenix definition of biochemical failure, with a median prostate-specific antigen nadir of 0.19ng/mL. Three men have reported grade 2 late genitourinary toxicity. There has been no report of grade 3-5 toxicity. CONCLUSION: Transperineal ultrasound-guided HDR brachytherapy using the above technique should be considered as definitive therapy for patients with localized prostate cancer and a prior history of APR and pelvic EBRT.

Successful treatment of high risk and recurrent pediatric desmoids using radiation as a component of multimodality therapy.

PURPOSE: To evaluate the role of radiation therapy (RT) as a component of multimodality therapy for pediatric desmoids. METHODS AND MATERIALS: Twenty-one children diagnosed between 1987 and 2005 were identified. Median age at start of treatment was 13 years (range, 2-21). Primary therapy consisted of resection alone (10), resection + external beam radiation therapy (EBRT) (5), resection + chemotherapy (CT; 3), EBRT alone (1), and CT alone (2). RESULTS: The median follow-up from start of treatment is 75.7 months (range, 16-162). Examining patients with gross total resections (GTRs) (-) margins and those who had GTRs (+) margins followed by EBRT, only 2 of 7 failed primary treatment. Conversely, 13 of 14 patients with other primary treatments failed locally. Of the 15 patients who recurred, only 1 patient had a GTR (-) margins. Seven of these patients had salvage therapy that did not include RT, and of these only 2 have no evidence of disease (NED) at last follow-up. In contrast, the remaining 8 patients received RT as a component of their final salvage therapy and 7 of these are NED at last follow-up. At last follow-up, no patient has died, although toxicities of therapy have occurred. CONCLUSIONS: Local control is difficult to achieve in pediatric patients with desmoids. In the setting in which negative surgical margins cannot be achieved, RT plays a key role in achieving NED status. Even after multiple recurrences, successful salvage is achievable, particularly when high-dose focal therapy is incorporated.

Comparison of dosimetric and biologic effective dose parameters for prostate and urethra using 131 Cs and 125 I for prostate permanent implant brachytherapy.

PURPOSE: To compare the urethral and prostate absolute and biologic effective doses (BEDs) for 131 Cs and 125 I prostate permanent implant brachytherapy (PPI). METHODS AND MATERIALS: Eight previously implanted manually planned 125 I PPI patients were replanned manually with 131 Cs, and re-planned using Inverse Planning Simulated Annealing. 131 Cs activity and the prescribed dose (115 Gy) were determined from that recommended by IsoRay. The BED was calculated for the prostate and urethra using an alpha/beta ratio of 2 and was also calculated for the prostate using an alpha/beta ratio of 6 and a urethral alpha/beta ratio of 2. The primary endpoints of this study were the prostate D90 BED (pD90BED) and urethral D30 BED normalized to the maximal potential prostate D90 BED (nuD30BED). RESULTS: The manual plan comparison (alpha/beta = 2) yielded no significant difference in the prostate D90 BED (median, 192 Gy2 for both isotopes). No significant difference was observed for the nuD30BED (median, 199 Gy2 and 202 Gy2 for 125 I and 131 Cs, respectively). For the inverse planning simulated annealing plan comparisons (alpha/beta = 2), the prostate D90 BED was significantly lower with 131 Cs than with 125 I (median, 177 Gy2 vs. 187 Gy2, respectively; p = 0.01). However, the nuD30BED was significantly greater with 131 Cs than with 125 I (median, 192 Gy2 vs. 189 Gy2, respectively; p = 0.01). Both the manual and the inverse planning simulated annealing plans resulted in a significantly lower prostate D90 BED (p = 0.01) and significantly greater nuD30BED for 131 Cs (p = 0.01), compared with 125 I, when the prostate alpha/beta ratio was 6 and the urethral alpha/beta ratio was 2. CONCLUSION: This report highlights the controversy in comparing the dose to both the prostate and the organs at risk with different radionuclides.

Radiotherapy using a water bath in the treatment of Bowen's disease of the digit.

PURPOSE: Bowen's disease (BD), a form of squamous cell carcinoma in situ, can transform into invasive squamous cell carcinoma and should be treated aggressively. Although standard treatment for BD is electrodessication and curettage, radiotherapy (RT) can be used for those patients who are poor surgical candidates or when surgery could result in a poor cosmetic and functional outcome. Surgical treatment of BD of the digit can result in poor function and sometimes amputation. Here, we report our experience using a unique water bath technique to treat BD of the digit. MATERIALS AND METHODS: This retrospective review evaluates the outcomes and toxicity of nine consecutive patients with BD of the digit treated with RT between 1999 and 2004. Fourteen digit lesions were immersed in a water bath and treated with photon irradiation. The median radiation dose delivered was 50Gy (range 25-66Gy) in 2.5Gy fractions (range 2-3Gy). RESULTS: The median age of the patients treated was 77 years (range 29-87 years). Three patients (33%) had more than one digit treated. With a median follow-up of 25 months (range 0.4-52 months), all 14 digit lesions are locally controlled. The majority of lesions demonstrated mild to moderate erythema, desquamation, or edema (grade 1-2) acutely following RT which resolved within one month of treatment. Two digits (14%) developed ulcers (grade 4) which healed following RT. The only long-term toxicity was decreased sensation and strength in one patient who had three circumferential lesions. This toxicity was limited and did not appear to influence the patient's daily activities (grade 2). CONCLUSIONS: These preliminary results demonstrate high rates of tumor control with minimal morbidity following definitive RT in the treatment of BD of the digit, and suggest that RT may be a viable treatment alternative to surgery for selected lesions. Through a multidisciplinary assessment, treatment of BD of the digit can be individualized to optimize patient care.

Matched case-control study of quality of life and xerostomia after intensity-modulated radiotherapy or standard radiotherapy for head-and-neck cancer: initial report.

PURPOSE: To compare quality of life (QOL) and xerostomia between head-and-neck cancer patients who received standard radiotherapy (RT) and patients matched by factors known to affect QOL who received intensity-modulated RT (IMRT). METHODS AND MATERIALS: This was a prospective, longitudinal study of patients with head-and-neck cancer requiring bilateral neck irradiation who received IMRT at the University of Michigan and patients who received standard RT at affiliated clinics. Each patient received a validated head-and-neck cancer-related QOL questionnaire (HNQOL) consisting of four multi-item domains--Eating, Communication, Pain, and Emotion--and a validated patient-reported xerostomia questionnaire (XQ). In both questionnaires, the answers were scored 0-100, with higher scores denoting worse QOL or xerostomia. The questionnaires were given before therapy and at 1, 3, 6, 12, 18, and 24 months after the completion of therapy. Each standard RT patient was matched with several IMRT patients according to tumor site, stage, RT status (postoperative or definitive), and age. A linear mixed-effects model was fit to compare outcomes between the two treatment groups and to model trends over time. To account for matching, the differences in scores between the matched sets of patients were fit as a random intercept. Also, matching was taken into account in the model by using the standard error of the within-paired-groups differences. RESULTS: Between 1997 and 2002, 10 patients who had received standard RT and answered the XQ and HNQOL through at least 1 year were included in the study. Each of these patients was matched with a subgroup of 2-5 patients (median, 3) who had received IMRT, had similar patient and tumor characteristics, and answered the same questionnaires. A total of 30 patients were included in the IMRT group. During the initial months after therapy, the XQ and HNQOL summary scores worsened significantly in both groups compared with the pretherapy scores. Starting at 6 months, improvements of both XQ and HNQOL scores were found over time in the IMRT patients (p = 0.01 and 0.04, respectively), compared with no trend of improvement in the standard RT patients (p = 0.5 and 0.9, respectively). The trend of improvement over time in QOL in the IMRT patients was noted in most of the HNQOL domains (Eating: p = 0.07, Pain: p = 0.05, Emotion: p = 0.04, and Communication: p = 0.13), compared with no trend of improvement in most of the domains in the standard RT patients. As the scores of the IMRT (but not the standard RT) patients improved over time, the differences between the groups in the mean XQ and HNQOL summary scores widened. At 12 months, median XQ and HNQOL scores were lower (better) in the IMRT compared with the standard RT patients by 19 and 20 points, respectively, adjusted for the pretherapy values (p = 0.2). In both groups, the pretherapy XQ and HNQOL summary scores were significantly related to the respective posttherapy scores (p = 0.02 and p < 0.01, respectively). CONCLUSIONS: After initial posttherapy declines in both groups, xerostomia and QOL improved over time after IMRT but not after standard RT. The potential benefits gained from IMRT in xerostomia or in QOL, compared with standard RT, are best reflected late (> or = 6 months) after therapy.

Predictive factors of local-regional recurrences following parotid sparing intensity modulated or 3D conformal radiotherapy for head and neck cancer.

BACKGROUND AND PURPOSE: Predictive factors for local-regional (LR) failures after parotid-sparing, Intensity modulated (IMRT) or 3D conformal radiotherapy for head and neck (HN) cancers were assessed. PATIENTS AND METHODS: One hundred and fifty-eight patients with mostly stages III-IV HN squamous cell carcinoma underwent curative bilateral neck irradiation aimed at sparing the parotid glands. Patient, tumor, and treatment factors were analyzed as predictive factors for LR failure. RESULTS: Twenty-three patients had LR recurrence (19 in-field and four marginal). No differences were found in the doses delivered to the PTVs of patients with or without in-field recurrences. In univariate analysis, tumor site was highly predictive for LR failure in both postoperative and definitive RT patients. In postoperative RT patients, pathologic tumor size, margin status, extracapsular extension (ECE) and number of lymph node metastases, were also significantly predictive. Multivariate analysis showed tumor site (oropharynx vs. other sites) to be a significant predictor in all patients, and involved margins and number of involved lymph nodes in postoperative patients. CONCLUSIONS: Clinical rather than dosimetric factors predicted for LR failures in this series, and were similar to those reported following standard RT. These factors may aid in the selection of patients for studies of treatment intensification using IMRT.

Metabolic abnormalities associated with weight loss during chemoirradiation of head-and-neck cancer.

PURPOSE: Weight loss caused by acute mucositis and dysphagia is common during concurrent chemoirradiation (chemo-RT) of head-and-neck (HN) cancer. The metabolic consequences of weight loss during chemo-RT were investigated. PATIENTS AND METHODS: Ninety-six patients with locally advanced HN cancer were treated from 1995 to 2001 on protocols that consisted of 1 to 2 cycles of induction cisplatin/5-fluorouracil followed by irradiation (70 Gy over 7 weeks) concurrent with cisplatin (100 mg/m2 every 3 weeks). Body weights and metabolic evaluations were obtained before and during induction chemotherapy and chemo-RT. Greatest percent changes in weight and in the laboratory values were calculated for each phase of therapy. RESULTS: During induction chemotherapy, significant changes were found in BUN, BUN:creatinine ratio, HCO3, Mg, and albumin, but not in creatinine, Na, K, or weight. During chemo-RT, significant additional changes were observed in all parameters measured, including increases in BUN, creatinine, BUN: creatinine ratio, and HCO3 and decreases in Mg, albumin, Na, K, and weight. The magnitude of most of these changes was significantly greater during chemo-RT than during induction chemotherapy. During chemo-RT, 35% of the patients had more than 10% body weight loss and 6 patients had an increase in creatinine of more than 100%, including 5 patients with Grade 2 nephrotoxicity, all of whom had weight loss 10% or more. Significant correlations were found between weight loss and creatinine (p < 0.0001) or BUN (p = 0.0002) rises, but not with BUN:creatinine ratio or other metabolic changes. Age, gender, tobacco history, hypertension, and diabetes mellitus were not significant predictors of nephrotoxicity. CONCLUSIONS: Weight loss during cisplatin-containing chemo-RT was found to be associated with reduced kidney function. These findings do not establish cause-effect relationships; however, they highlight the importance of intensive supportive measures of nutrition and hydration beyond standard hydration during cisplatin administration. These intensive measures should be enacted before a 10% weight loss is reached.