Dose escalation for Prostate Cancer

10 year results of the PROG trial of proton dose escalation for low-intermediate risk prostate cancer are published in the weeks JCO. No big surprises, the same trends hold with improvements in biochemical control, no difference in OS (though a 5% trend does exist favoring high dose). The 10 year data does solidify support of dose escalation, and the lack of delayed toxicity is quite encouraging.

Link and abstract

Randomized Trial Comparing Conventional-Dose With High-Dose Conformal Radiation Therapy in Early-Stage Adenocarcinoma of the Prostate: Long-Term Results From Proton Radiation Oncology Group/American College of Radiology 95-09 [Genitourinary Cancer]:

"Purpose

To test the hypothesis that increasing radiation dose delivered to men with early-stage prostate cancer improves clinical outcomes.
Patients and Methods

Men with T1b-T2b prostate cancer and prostate-specific antigen ≤ 15 ng/mL were randomly assigned to a total dose of either 70.2 Gray equivalents (GyE; conventional) or 79.2 GyE (high). No patient received androgen suppression therapy with radiation. Local failure (LF), biochemical failure (BF), and overall survival (OS) were outcomes.
Results

A total of 393 men were randomly assigned, and median follow-up was 8.9 years. Men receiving high-dose radiation therapy were significantly less likely to have LF, with a hazard ratio of 0.57. The 10-year American Society for Therapeutic Radiology and Oncology BF rates were 32.4% for conventional-dose and 16.7% for high-dose radiation therapy (P < .0001). This difference held when only those with low-risk disease (n = 227; 58% of total) were examined: 28.2% for conventional and 7.1% for high dose (P < .0001). There was a strong trend in the same direction for the intermediate-risk patients (n = 144; 37% of total; 42.1% v 30.4%, P = .06). Eleven percent of patients subsequently required androgen deprivation for recurrence after conventional dose compared with 6% after high dose (P = .047). There remains no difference in OS rates between the treatment arms (78.4% v 83.4%; P = .41). Two percent of patients in both arms experienced late grade ≥ 3 genitourinary toxicity, and 1% of patients in the high-dose arm experienced late grade ≥ 3 GI toxicity.
Conclusion

This randomized controlled trial shows superior long-term cancer control for men with localized prostate cancer receiving high-dose versus conventional-dose radiation. This was achieved without an increase in grade ≥ 3 late urinary or rectal morbidity.
"

SBRT vs Wedge resection (retrospective)

This weeks JCO:

A retrospective comparison of wedge resection and SBRT for stage I NSCLC is reported by Beaumont. They find improved local and regional recurrence rates with SBRT, similar cause specific survival, and worse OS in with SBRT. They explain the worse OS by patient selection (i.e. the healthier patients were taken for wedge).

I think from this, you see a signal that SBRT seems at least equivalent to wedge and potentially less toxic. I think it is hard to say that it is superior for local control, because if one is censoring out the patients who die (as one does in with the local control endpoint), the more patients die from other causes, the less events are possible for local failure. Thus the LRC may have been higher with SBRT due to the lower OS. In addition the followup was not as long for SBRT patients.

Regardless, this is an interesting paper, and supports the use of SBRT in medically inoperable patients.

Link and Abstract:

Outcomes After Stereotactic Lung Radiotherapy or Wedge Resection for Stage I Non-Small-Cell Lung Cancer [Thoracic Oncology]: "Purpose

To compare outcomes between lung stereotactic radiotherapy (SBRT) and wedge resection for stage I non–small-cell lung cancer (NSCLC).

Patients and Methods

One hundred twenty-four patients with T1-2N0 NSCLC underwent wedge resection (n = 69) or image-guided lung SBRT (n = 58) from February 2003 through August 2008. All were ineligible for anatomic lobectomy; of those receiving SBRT, 95% were medically inoperable, with 5% refusing surgery. Mean forced expiratory volume in 1 second and diffusing capacity of lung for carbon monoxide were 1.39 L and 12.0 mL/min/mmHg for wedge versus 1.31 L and 10.14 mL/min/mmHg for SBRT (P = not significant). Mean Charlson comorbidity index and median age were 3 and 74 years for wedge versus 4 and 78 years for SBRT (P < .01, P = .04). SBRT was volumetrically prescribed as 48 (T1) or 60 (T2) Gy in four to five fractions.

Results

Median potential follow-up is 2.5 years. At 30 months, no significant differences were identified in regional recurrence (RR), locoregional recurrence (LRR), distant metastasis (DM), or freedom from any failure (FFF) between the two groups (P > .16). SBRT reduced the risk of local recurrence (LR), 4% versus 20% for wedge (P = .07). Overall survival (OS) was higher with wedge but cause-specific survival (CSS) was identical. Results excluding synchronous primaries, nonbiopsied tumors, or pathologic T4 disease (wedge satellite lesion) showed reduced LR (5% v 24%, P = .05), RR (0% v 18%, P = .07), and LRR (5% v 29%, P = .03) with SBRT. There were no differences in DM, FFF, or CSS, but OS was higher with wedge.

Conclusion

Both lung SBRT and wedge resection are reasonable treatment options for stage I NSCLC patients ineligible for anatomic lobectomy. SBRT reduced LR, RR, and LRR. In this nonrandomized population of patients selected for surgery versus SBRT (medically inoperable) at physician discretion, OS was higher in surgical patients. SBRT and surgery, however, had identical CSS.

"

Long-Term Results of Hypofractionated Radiation Therapy for Breast Cancer

In the NEJM this week:

10 year results of the Canadian Hypofractionation trial for breast cancer are published, showing no difference in local control, toxicity, or cosmetic appearance. Interestingly, a new subset analysis in this paper seems to suggest that high grade cancers were not the best candidate for hypofractionation due to a higher failure rate. However in a low risk patient, this has become a standard option at Duke for the treatment of node-megative disease. Of course the caveats is that this trial does not apply to patients who are node positive and in those who have a separation >25cm. Boost was not also used in the trial; though we will occasionally offer a boost of 200cGy x 5 with the 2.66Gy x 16fx regimen extrapolating from the boost trials.

Link to the NEJM:

Long-Term Results of Hypofractionated Radiation Therapy for Breast Cancer: "The optimal schedule of radiation treatment after breast-conserving surgery for invasive breast cancer is unknown. In this study, two groups of patients received either hypofractionated radiation or a standard schedule of radiation treatment. Ten years later, the two groups had similar risks of local recurrence and a similar appearance of the breast."

[Articles] Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial

This weeks Lancet:

An interesting article on the potential utility for MRI in initial work up of breast cancer. While a prior trial in the NEJM (link) demonstrated that one could detect occult cancers in the contralateral breast in 3% of patients (by biopsying 12%), this trial looked at the utility of MRI in surgical planning in the ipsilateral breast. The short of it: no difference in reoperation rates for positive or close margins. MRI seems to becoming more of a standard preoperative test, however the only clinically relevant outcome reported as yet is an increase in the mastectomy rate (link).

Link to the Lancet

[Articles] Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomised controlled trial: "MRI might improve diagnosis of breast cancer, reducing rates of reoperation. We assessed the clinical efficacy of contrast-enhanced MRI in women with primary breast cancer."

Induction Chemo for Rectal Cancer

This weeks JCO has a randomized phase II study examining induction chemotherapy for rectal cancer. The endpoint was pCR, a reasonable surrogate for clinical outcome.

Randomized phase II studies are always a bit of an enigma to me. They are not powered to show differences between the arms (that would be a phase III), and yet they are randomized. The practical significance is that it is much easier to get these done because the accrual goals are much lower than a true phase III. In this case, the goals of the researchers was to "drop" a less effective arm, i.e. assuming that the better arm would have a pCR rate of 15%, they had 90% power to detect a difference if the worse arm was 10%.

Either way, their results are similar to what has been seen in other induction trials for solid tumors, no differences in the clinically significant disease endpoints. What they did show is better tolerance of the chemotherapy, and thus more exposure to drug. One other thing that is obviously important is to look for the ability to deliver radiation and go to surgery afterwards, which fortunately was no different between the arms.

They conclude that it was reasonable to move onto phase III comparing these approaches.

Link and Abstract:

Phase II, Randomized Study of Concomitant Chemoradiotherapy Followed by Surgery and Adjuvant Capecitabine Plus Oxaliplatin (CAPOX) Compared With Induction CAPOX Followed by Concomitant Chemoradiotherapy and Surgery in Magnetic Resonance Imaging-Defined, Locally Advanced Rectal Cancer: Grupo Cancer de Recto 3 Study [Gastrointestinal Cancer]: "Purpose

The optimal therapeutic sequence of the adjuvant chemotherapy component of preoperative chemoradiotherapy (CRT) for patients with locally advanced rectal cancer is controversial. Induction chemotherapy before preoperative CRT may be associated with better efficacy and compliance.

Patients and Methods

A total of 108 patients with locally advanced rectal cancer were randomly assigned to arm A—preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)—or arm B—induction CAPOX followed by CRT and surgery. The primary end point was pathologic complete response rate (pCR).

Results

On an intention-to-treat basis, the pCR for arms A and B were 13.5% (95% CI, 5.6% to 25.8%) and 14.3% (95% CI, 6.4% to 26.2%), respectively. There were no statistically significant differences in other end points, including downstaging, tumor regression, and R0 resection. Overall, chemotherapy treatment exposure was higher in arm B than in arm A for both oxaliplatin (P < .0001) and capecitabine (P < .0001). During CRT, grades 3 to 4 adverse events were similar in both arms but were significantly higher in arm A during postoperative adjuvant CT than with induction CT in arm B. There were three deaths in each arm during the treatment period.

Conclusion

Compared with postoperative adjuvant CAPOX, induction CAPOX before CRT had similar pCR and complete resection rates. It did achieve more favorable compliance and toxicity profiles. On the basis of these findings, a phase III study to definitively test the induction strategy is warranted."

Cancer During Pregnancy: An Analysis of 215 Patients Emphasizing the Obstetrical and the Neonatal Outcomes [Gynecologic Cancer]

This weeks JCO -

An interesting report on outcomes for patients treated for malignancy with surgery, chemotherapy, and or radiation. The numbers are small for radiation; largely the focus is on cytotoxic treatments. The data however is invaluable to clinicians and patients that find themselves in this challenging situation.

Link and Abstract.

Cancer During Pregnancy: An Analysis of 215 Patients Emphasizing the Obstetrical and the Neonatal Outcomes [Gynecologic Cancer]: "Purpose

The aim of this study was to assess the management and the obstetrical and neonatal outcomes of pregnancies complicated by cancer.

Patients and Methods

In an international collaborative setting, patients with invasive cancer diagnosed during pregnancy between 1998 and 2008 were identified. Clinical data regarding the cancer diagnosis and treatment and the obstetric and neonatal outcomes were collected and analyzed.

Results

Of 215 patients, five (2.3%) had a pregnancy that ended in a spontaneous miscarriage and 30 (14.0%) pregnancies were interrupted. Treatment was initiated during pregnancy in 122 (56.7%) patients and postpartum in 58 (27.0%) patients. The most frequently encountered cancer types were breast cancer (46%), hematologic malignancies (18%), and dermatologic malignancies (10%). The mean gestational age at delivery was 36.3 ± 2.9 weeks. Delivery was induced in 71.7% of pregnancies, and 54.2% of children were born preterm. In the group of patients prenatally exposed to cytotoxic treatment, the prevalence of preterm labor was increased (11.8%; P = .012). Furthermore, in this group a higher proportion of small-for-gestational-age children (birth weight below 10th percentile) was observed (24.2%; P = .001). Of all neonates, 51.2% were admitted to a neonatal intensive care unit, mainly (85.2%) because of prematurity. There was no increased incidence of congenital malformations.

Conclusion

Pregnant cancer patients should be treated in a multidisciplinary setting with access to maternal and neonatal intensive care units. Prevention of iatrogenic prematurity appears to be an important part of the treatment strategy."

Pregabalin (Lyrica) for Hot Flashes

This weeks JCO - Pregabalin (trade name Lyrica) is a new drug on the market for depression and neuropathic pain. It also is studied for reduction in hot flashes; a common problem for those with either breast or prostate cancer. This study demonstrates efficacy with a dose of 75mg BID. Wether it is more or less effective than other measures is unknown.

Link and Abstract

Phase III, Randomized, Double-Blind, Placebo-Controlled Evaluation of Pregabalin for Alleviating Hot Flashes, N07C1 [Palliative and Supportive Care]: "Purpose

Hot flashes are a common problem for which effective and safe treatments are needed. The current trial was conducted on the basis of preliminary promising data that pregabalin decreased hot flashes.

Patients and Methods

A double-blind, placebo-controlled, randomized trial design was used to compare pregabalin at target doses of 75 mg twice daily and 150 mg twice daily with a placebo. Hot flash frequencies and scores (frequency times mean severity) were recorded daily during a baseline week and for six treatment weeks. The primary end point for this study was the change-from-baseline hot flash score during treatment week 6 between the 150 mg twice daily target pregabalin treatment and placebo. Nonparametric Wilcoxon rank sum tests, two-sample t tests, and ² tests were used to compare the primary and secondary hot flash efficacy end points between pregabalin treatments and placebo.

Results

Hot flash score changes available for 163 patients during the sixth treatment week compared with a baseline week decreased by 50%, 65%, and 71% in the placebo, and target 75 mg twice daily and 150 mg twice daily pregabalin arms, respectively (P = .009 and P = .007, comparing respective pregabalin arms to the placebo arm). While some toxicities were significantly more common in the pregabalin arms, being more evident with the higher dose, pregabalin was generally well tolerated by most patients.

Conclusion

Pregabalin decreases hot flashes and is reasonably well tolerated. A target dose of 75 mg twice daily is recommended. Its effects appear to be roughly comparable to what has been reported with gabapentin and with some newer antidepressants."

Venlafaxine, medroxyprogesterone acetate, and cyproterone acetate for Hot Flushes in Men taking GNrH analogues

An interesting phase III trial looking at options for treating hot flushes in men recieving androgren deprivation for prostate cancer. The short - all reduced hot flushes, but cyproterone and medroxyprogesterone were superior. The authors conclude that medroxyprogesterone 20mg daily is the perferred treatment, as cyproterone also has an effect on the treatment of prostate cancer and as such may confound the overall management of the prostate cancer. In the US megestrol (Megace) may be preferable, but was not used in this trial as it was not available for use in France.

Link:

[Articles] Efficacy of venlafaxine, medroxyprogesterone acetate, and cyproterone acetate for the treatment of vasomotor hot flushes in men taking gonadotropin-releasing hormone analogues for prostate cancer: a double-blind, randomised trial: "Hot flushes are the most common complaints reported by men undergoing androgen suppression treatment for prostate cancer. We designed a randomised double-blind trial to compare the efficacy of three drugs, each of which has proven effective for preventing hot flushes in previous studies."

HeLa Cell Line in Wired

Wired has a nice little "gee whiz" article on the history of the HeLa cell line this month.

Link: http://www.wired.com/magazine/2010/01/st_henrietta/

Post Op prostate bed contouring atlas

This weeks red journal - A consensus atlas is designed for the RTOG in postop prostate. For the atlas follow this link:http://goo.gl/et6F

For the Article:

Development of RTOG Consensus Guidelines for the Definition of the Clinical Target Volume for Postoperative Conformal Radiation Therapy for Prostate Cancer: "Purpose: To define a prostate fossa clinical target volume (PF-CTV) for Radiation Therapy Oncology Group (RTOG) trials using postoperative radiotherapy for prostate cancer.Methods and Materials: An RTOG-sponsored meeting was held to define an appropriate PF-CTV after radical prostatectomy. Data were presented describing radiographic failure patterns after surgery. Target volumes used in previous trials were reviewed. Using contours independently submitted by 13 radiation oncologists, a statistical imputation method derived a preliminary “consensus” PF-CTV.Results: Starting from the model-derived CTV, consensus was reached for a CT image–based PF-CTV. The PF-CTV should extend superiorly from the level of the caudal vas deferens remnant to >8–12 mm inferior to vesicourethral anastomosis (VUA). Below the superior border of the pubic symphysis, the anterior border extends to the posterior aspect of the pubis and posteriorly to the rectum, where it may be concave at the level of the VUA. At this level, the lateral border extends to the levator ani. Above the pubic symphysis, the anterior border should encompass the posterior 1–2 cm of the bladder wall; posteriorly, it is bounded by the mesorectal fascia. At this level, the lateral border is the sacrorectogenitopubic fascia. Seminal vesicle remnants, if present, should be included in the CTV if there is pathologic evidence of their involvement.Conclusions: Consensus on postoperative PF-CTV for RT after prostatectomy was reached and is available as a CT image atlas on the RTOG website. This will allow uniformity in defining PF-CTV for clinical trials that include postprostatectomy RT."

Association of the Recurrence Score (Oncotype DX) with Local Recurrence

Online in the JCO:

The recurrence score (oncotype DX) has been an extremely valuable tool in decision making for the delivery of systemic therapy in node negative, ER+ breast cancer. The primary analyses published to date describe it's association with distant failure, survival and the relative benefit of cytotoxic chemotherapy. This article describes the association of this score with loco-regional recurrence, of upmost interest to radiation oncologists as we move to an era of personalized medicine. Perhaps not surprisingly, an association is indeed found. Of course whether radiation should be intensified somehow in the higher risk patients, or de-intensified in the lower risk patients is something that this report cannot address, but does open up the door to some potentially quite interesting clinical questions to test prospectively....

Link

Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival

The "Bonner" trial reports five year data in this months Lancet Oncology. The initial survival benefit is continued out to longer follow up than the prior NEJM article. A subgroup analysis also demonstrates that in those recieving cetuximab, the development of a more severe acneiform rash was associated with an improved survival. This finding is similar to prior reports in colon cancer. What is causing this is unknown, but it may be a surrogate for reaching systemic drug levels...

Link -

[Articles] Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival: "Previous results from our phase 3 randomised trial showed that adding cetuximab to primary radiotherapy increased overall survival in patients with locoregionally advanced squamous-cell carcinoma of the head and neck (LASCCHN) at 3 years. Here we report the 5-year survival data, and investigate the relation between cetuximab-induced rash and survival."

Phase I Study of Accelerated Conformal Radiotherapy for Stage I NSCLC

This weeks JCO:

The results of the CALGB 39904 trial are published after multiple abstract presentations. This was looking at an alternative to SBRT in the treatment of early stage NSCLC, increasing the intensity of treatment, while keeping the nominal dose stable at 70Gy. The results are encouraging, however, SBRT has probably already lapped this style of RT for this patient population.

Link and Abstract

Phase I Study of Accelerated Conformal Radiotherapy for Stage I Non-Small-Cell Lung Cancer in Patients With Pulmonary Dysfunction: CALGB 39904 [Thoracic Oncology]: "Purpose

The optimal treatment for medically inoperable stage I non–small-cell lung cancer (NSCLC) has not been defined.

Patients and Methods

Cancer and Leukemia Group B trial 39904 prospectively assessed accelerated, once-daily, three-dimensional radiotherapy for early-stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 or T2N0 NSCLC (< 4 cm) and pulmonary dysfunction. The nominal total radiotherapy dose remained at 70 Gy, while the number of daily fractions in each successive cohort was reduced.

Results

Thirty-nine eligible patients were accrued (eight patients each on cohorts 1 to 4 and seven patients on cohort 5) between January 2001 and July 2005. One grade 3 nonhematologic toxicity was observed in both cohort 3 (dyspnea) and cohort 4 (pain). The major response rate was 77%. After a median follow-up time of 53 months, the actuarial median survival time of all eligible patients was 38.5 months. Local relapse was observed in three patients.

Conclusion

Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further investigation of this approach is warranted.

"

Radiation Pneumonitis after Radiotherapy for Breast Cancer

the NEJM of the week has a good example of radiation pneumonitis

Link-

Radiation Pneumonitis after Radiotherapy for Breast Cancer:

Adjuvant Chemotherapy for NSCLC, updates on two influential trials

JCO this week: Two of the more influencial trials on adjuvant chemotherapy for resected NSCLC are updated, the JBR-10 and the IALT studies. The JBR-10 study continues to show a survival benefit out to almost 10 years, though the stage IBs seemed not to benefit. The IALT study continued to demonstrate a DFS benefit, but the OS figures had slipped to non-significance.

Links and abstracts:

Randomized Phase III Trial of Vinorelbine Plus Cisplatin Compared With Observation in Completely Resected Stage IB and II Non-Small-Cell Lung Cancer: Updated Survival Analysis of JBR-10 [Thoracic Oncology]: "Purpose

Adjuvant cisplatin-based chemotherapy (ACT) is now an accepted standard for completely resected stage II and III A non–small-cell lung cancer (NSCLC). Long-term follow-up is important to document persistent benefit and late toxicity. We report here updated overall survival (OS) and disease-specific survival (DSS) data.

Patients and Methods

Patients with completely resected stage IB (T2N0, n = 219) or II (T1-2N1, n = 263) NSCLC were randomly assigned to receive 4 cycles of vinorelbine/cisplatin or observation. All efficacy analyses were performed on an intention-to-treat basis.

Results

Median follow-up was 9.3 years (range, 5.8 to 13.8; 33 lost to follow-up); there were 271 deaths in 482 randomly assigned patients. ACT continues to show a benefit (hazard ratio [HR], 0.78; 95% CI, 0.61 to 0.99; P = .04). There was a trend for interaction with disease stage (P = .09; HR for stage II, 0.68; 95% CI, 0.5 to 0.92; P = .01; stage IB, HR, 1.03; 95% CI, 0.7 to 1.52; P = .87). ACT resulted in significantly prolonged DSS (HR, 0.73; 95% CI, 0.55 to 0.97; P = .03). Observation was associated with significantly higher risk of death from lung cancer (P = .02), with no difference in rates of death from other causes or second primary malignancies between the arms.

Conclusion

Prolonged follow-up of patients from the JBR.10 trial continues to show a benefit in survival for adjuvant chemotherapy. This benefit appears to be confined to N1 patients. There was no increase in death from other causes in the chemotherapy arm."

Long-Term Results of the International Adjuvant Lung Cancer Trial Evaluating Adjuvant Cisplatin-Based Chemotherapy in Resected Lung Cancer [Thoracic Oncology]

Purpose

Based on 5-year or shorter-term follow-up data in recent randomized trials, adjuvant cisplatin-based chemotherapy is now generally recommended after complete surgical resection for patients with non–small-cell lung cancer (NSCLC). We evaluated the results of the International Adjuvant Lung Cancer Trial study with three additional years of follow-up.

Patients and Methods

Patients with completely resected NSCLC were randomly assigned to three or four cycles of cisplatin-based chemotherapy or to observation. Cox models were used to evaluate treatment effect according to follow-up duration.

Results

The trial included 1,867 patients with a median follow-up of 7.5 years. Results showed a beneficial effect of adjuvant chemotherapy on overall survival (hazard ratio [HR], 0.91; 95% CI, 0.81 to 1.02; P = .10) and on disease-free survival (HR, 0.88; 95% CI, 0.78 to 0.98; P = .02). However, there was a significant difference between the results of overall survival before and after 5 years of follow-up (HR, 0.86; 95% CI, 0.76 to 0.97; P = .01 v HR, 1.45; 95% CI, 1.02 to 2.07; P = .04) with P = .006 for interaction. Similar results were observed for disease-free survival. The analysis of non-lung cancer deaths for the whole period showed an HR of 1.34 (95% CI, 0.99 to 1.81; P = .06).

Conclusion

These results confirm the significant efficacy of adjuvant chemotherapy at 5 years. The difference in results beyond 5 years of follow-up underscores the need for the long-term follow-up of other adjuvant lung cancer trials and for a better identification of patients deriving long-term benefit from adjuvant chemotherapy.

Results in stage I, II LPHD

A retrospective study from Dana-Farber reports on outcomes from LPHD (lymphocyte predominant Hodgkin's disease). They report excellent 10yr results with limited field RT. Chemotherapy alone resulted in poor PFS, however most were salvaged. Larger fields did not appear to improve results.

Link and Abstract:

Early-Stage, Lymphocyte-Predominant Hodgkin's Lymphoma: Patient Outcomes From a Large, Single-Institution Series With Long Follow-Up [Hematologic Malignancies]: "Purpose

The optimal treatment for early-stage, lymphocyte-predominant Hodgkin's lymphoma (LPHL) is not well defined. Treatment has become less aggressive over time in an attempt to reduce iatrogenic complications, such as cardiac mortality and second cancers, but long-term efficacy is unclear. We present the long-term outcome of patients treated at a single institution.

Patients and Methods

The study population includes 113 patients with stage I or II LPHL treated between 1970 and 2005. Pathologic diagnosis for all patients was confirmed using standard criteria. Ninety-three patients received radiation therapy (RT) alone, 13 received RT with chemotherapy, and seven received chemotherapy alone. Among patients treated with RT, 25 received limited-field, 35 received regional-field, and 46 received extended-field RT.

Results

Median follow-up was 136 months. Ten-year progression-free survival (PFS) rates were 85% (stage I) and 61% (stage II); overall survival (OS) rates were 94% and 97% for stages I and II, respectively. PFS and OS did not differ among patients who received limited-field, regional-field, or extended-field RT. In contrast, six of seven patients who received chemotherapy alone without RT developed early disease progression and required salvage treatment. Multivariable analysis adjusting for extent of RT, clinical stage, sex, and use of chemotherapy confirmed that the extent of RT was not significantly associated with PFS (P = .67) or OS (P = .99). The addition of chemotherapy to RT did not improve PFS or OS compared with RT alone.

Conclusion

RT alone leads to sustained disease control and high long-term survival rates in patients with early-stage LPHL. This study supports the use of limited-field RT alone to treat this disease."

Active surveillance for Low risk Prostate Cancer

JCO this week:

A single arm study from Canada suggests that active surveillance is a reasonable option in low risk ACP. Though 50% of those that did undergo radical treatment ended up having PSA failure, it was only 13% of the overall cohort. That said the follow up remains a little short at just under seven years; I would like to see 10-15 year data reported due to the fact that often prostate cancer death occurs much later than detection or biochemical failure.

Link and Abstract

Clinical Results of Long-Term Follow-Up of a Large, Active Surveillance Cohort With Localized Prostate Cancer [Genitourinary Cancer]: "Purpose

We assessed the outcome of a watchful-waiting protocol with selective delayed intervention by using clinical prostate-specific antigen (PSA), or histologic progression as treatment indications for clinically localized prostate cancer.

Patients and Methods

This was a prospective, single-arm, cohort study. Patients were managed with an initial expectant approach. Definitive intervention was offered to those patients with a PSA doubling time of less than 3 years, Gleason score progression (to 4 + 3 or greater), or unequivocal clinical progression. Survival analysis and Cox proportional hazard model were applied to the data.

Results

A total of 450 patients have been observed with active surveillance. Median follow-up was 6.8 years (range, 1 to 13 years). Overall survival was 78.6%. The 10-year prostate cancer actuarial survival was 97.2%. Overall, 30% of patients have been reclassified as higher risk and have been offered definitive therapy. Of 117 patients treated radically, the PSA failure rate was 50%, which was 13% of the total cohort. PSA doubling time of 3 years or less was associated with an 8.5-times higher risk of biochemical failure after definitive treatment compared with a doubling time of more than 3 years (P < .0001). The hazard ratio for nonprostate cancer to prostate cancer mortality was 18.6 at 10 years.

Conclusion

We observed a low rate of prostate cancer mortality. Among the patients who were reclassified as higher risk and who were treated, PSA failure was relatively common. Other-cause mortality accounted for almost all of the deaths. Additional studies are warranted to improve the identification of patients who harbor more aggressive disease despite favorable clinical parameters at diagnosis."

Induction Cetuximab, Paclitaxel and Carboplatin in H&N cancers

JCO this week: MD Anderson reports the results of a Phase II combining cetuximab, paclitaxel and carboplatin before definitive surgery, radiation or chemoradiation. Interesting results, but obviously the overall question of whether induction is the best approach remains up in the air. Abstract and link:

Induction Chemotherapy and Cetuximab for Locally Advanced Squamous Cell Carcinoma of the Head and Neck: Results From a Phase II Prospective Trial [Head and Neck Cancer]: "Purpose

To determine the potential efficacy of combining cetuximab with chemotherapy in patients with advanced nodal disease, we conducted a phase II trial with induction chemotherapy (ICT) consisting of six weekly cycles of paclitaxel 135 mg/m² and carboplatin (area under the curve = 2) with cetuximab 400 mg/m² in week 1 and then 250 mg/m² (PCC).

Patients and Methods

Forty-seven previously untreated patients (41 with oropharynx primaries; 33 men, 14 women; median age, 53 years; performance status of 0 or 1) with squamous cell carcinoma of the head and neck (SCCHN; T1-4, N2b/c/3) were treated and evaluated for clinical and radiographic response. After ICT, patients underwent risk-based local therapy, which consisted of either radiation, concomitant chemoradiotherapy, or surgery, based on tumor stage and site at diagnosis.

Results

After induction PCC, nine patients (19%) achieved a complete response, and 36 patients (77%) achieved a partial response. The most common grade 3 or 4 toxicity was skin rash (45%), followed by neutropenia (21%) without fever. At a median follow-up time of 33 months, locoregional or systemic disease progression was observed in six patients. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 87% (95% CI, 78% to 97%) and 91% (95% CI, 84% to 99%), respectively. Human papillomavirus (HPV) 16, found in 12 (46%) of 26 biopsies, was associated with improved PFS (P = .012) and OS (P = .046).

Conclusion

ICT with weekly PCC followed by risk-based local therapy seems to be feasible, effective, and well tolerated. PFS is promising, and this sequential treatment strategy should be further investigated. Patients with HPV-positive tumors have an excellent prognosis."

soy and breast cancer survival.

For those that Had Tofurky for Thanksgiving Dinner like me:

from JAMA - abstract and link

Soy Food Intake and Breast Cancer Survival [Original Contribution]: "

Context Soy foods are rich in isoflavones, a major group of phytoestrogens that have been hypothesized to reduce the risk of breast cancer. However, the estrogen-like effect of isoflavones and the potential interaction between isoflavones and tamoxifen have led to concern about soy food consumption among breast cancer patients.

Objective To evaluate the association of soy food intake after diagnosis of breast cancer with total mortality and cancer recurrence.

Design, Setting, and Participants The Shanghai Breast Cancer Survival Study, a large, population-based cohort study of 5042 female breast cancer survivors in China. Women aged 20 to 75 years with diagnoses between March 2002 and April 2006 were recruited and followed up through June 2009. Information on cancer diagnosis and treatment, lifestyle exposures after cancer diagnosis, and disease progression was collected at approximately 6 months after cancer diagnosis and was reassessed at 3 follow-up interviews conducted at 18, 36, and 60 months after diagnosis. Annual record linkage with the Shanghai Vital Statistics Registry database was carried out to obtain survival information for participants who were lost to follow-up. Medical charts were reviewed to verify disease and treatment information.

Main Outcome Measures Total mortality and breast cancer recurrence or breast cancer–related deaths. Cox regression analysis was carried out with adjustment for known clinical predictors and other lifestyle factors. Soy food intake was treated as a time-dependent variable.

Results During the median follow-up of 3.9 years (range, 0.5-6.2 years), 444 deaths and 534 recurrences or breast cancer–related deaths were documented in 5033 surgically treated breast cancer patients. Soy food intake, as measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence. The hazard ratio associated with the highest quartile of soy protein intake was 0.71 (95% confidence interval [CI], 0.54-0.92) for total mortality and 0.68 (95% CI, 0.54-0.87) for recurrence compared with the lowest quartile of intake. The multivariate-adjusted 4-year mortality rates were 10.3% and 7.4%, and the 4-year recurrence rates were 11.2% and 8.0%, respectively, for women in the lowest and highest quartiles of soy protein intake. The inverse association was evident among women with either estrogen receptor–positive or –negative breast cancer and was present in both users and nonusers of tamoxifen.

Conclusion Among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence.

"

RT first or Chemo first in Anaplastic Glioma

In the JCO this week:

Randomized data in different sequences of RT and Chemo in anaplastic Chemo. The bottom line from my take is that there is no significant difference in outcome, but toxicity is worse with chemo first. It is puzzling then that the conclusions of the paper state "These data may allow recommending chemotherapy as first-line treatment of patients with anaplastic gliomas, including patients with AA." That seems a bit at odds with the data presented - i.e. when you have two arms with equivalent therapeutic outcome, toxicity should drive the treatment decision, clearly favoring RT. It was also designed as a superiority trial for chemotherapy first, not a non-inferiority trial, so really it surely doesn't prove that chemo is as effective as RT either.

Link and astract:

NOA-04 Randomized Phase III Trial of Sequential Radiochemotherapy of Anaplastic Glioma With Procarbazine, Lomustine, and Vincristine or Temozolomide [Neurooncology]: "Purpose

The standard of care for anaplastic gliomas is surgery followed by radiotherapy. The NOA-04 phase III trial compared efficacy and safety of radiotherapy followed by chemotherapy at progression with the reverse sequence in patients with newly diagnosed anaplastic gliomas.

Patients and Methods

Patients (N = 318) were randomly assigned 2:1:1 (A:B1:B2) to receive conventional radiotherapy (arm A); procarbazine, lomustine (CCNU), and vincristine (PCV; arm B1); or temozolomide (arm B2) at diagnosis. At occurrence of unacceptable toxicity or disease progression, patients in arm A were treated with PCV or temozolomide (1:1 random assignment), whereas patients in arms B1 or B2 received radiotherapy. The primary end point was time to treatment failure (TTF), defined as progression after radiotherapy and one chemotherapy in either sequence.

Results

Patient characteristics in the intention-to-treat population (n = 274) were balanced between arms. All histologic diagnoses were centrally confirmed. Median TTF (hazard ratio [HR] = 1.2; 95% CI, 0.8 to 1.8), progression-free survival (PFS; HR = 1.0; 95% CI, 0.7 to 1.3, and overall survival (HR = 1.2; 95% CI, 0.8 to 1.9) were similar for arms A and B1/B2. Extent of resection was an important prognosticator. Anaplastic oligodendrogliomas and oligoastrocytomas share the same, better prognosis than anaplastic astrocytomas. Hypermethylation of the O⁶-methylguanine DNA-methyltransferase (MGMT) promoter (HR = 0.59; 95% CI, 0.36 to 1.0), mutations of the isocitrate dehydrogenase (IDH1) gene (HR = 0.48; 95% CI, 0.29 to 0.77), and oligodendroglial histology (HR = 0.33; 95% CI, 0.2 to 0.55) reduced the risk of progression. Hypermethylation of the MGMT promoter was associated with prolonged PFS in the chemotherapy and radiotherapy arm.

Conclusion

Initial radiotherapy or chemotherapy achieved comparable results in patients with anaplastic gliomas. IDH1 mutations are a novel positive prognostic factor in anaplastic gliomas, with a favorable impact stronger than that of 1p/19q codeletion or MGMT promoter methylation."